Diagnostics & Mitigation

As per the FDA, In vitro diagnostic (IVD) devices are tests performed on samples taken from the human body, such as swabs of mucus from inside the nose or back of the throat, or blood taken from a vein or fingerstick. IVDs can detect diseases or other conditions and can be used to monitor a person’s overall health to help cure, treat, or prevent diseases. There are several types of SARS-CoV-2 and COVID-19 related IVDs:

  • Diagnostic Tests – Tests that detect parts of the SARS-CoV-2 virus and can be used to diagnose infection with the SARS-CoV-2 virus. These include molecular tests and antigen tests.
  • Serology/Antibody Tests – Tests that detect antibodies (e.g., IgM, IgG) to the SARS-CoV-2 virus. Serology/antibody tests cannot be used to diagnose a current infection.
  • Tests for Management of COVID-19 Patients – Beyond tests that diagnose or detect SARS-CoV-2 virus or antibodies, there are also tests that are authorized for use in the management of patients with COVID-19, such as to detect biomarkers related to inflammation. Once patients are diagnosed with COVID-19 disease, these additional tests can be used to inform patient management decisions.

As on November 24, 2020, the FDA has authorized 291 tests under EUAs; these include 225 molecular tests, 59 antibody tests, and 7 antigen tests.


  • Antigen rapid tests, nasopharyngeal PCR and saliva PCR to detect SARS-CoV-2: a prospective comparative clinical trial [Link] (11/25/20)
  • Beckman Coulter launches its semi-quantitative SARS-CoV-2 IgG II antibody test  [Link] (11/25/20)
  • Sensitive quantitative detection of SARS-CoV-2 in clinical samples using digital warm-start CRISPR assay [Link] (11/25/20)
  • Rensselaer-developed algorithm accurately predicts COVID-19 patient outcomes [Link] (11/25/20)
  • Testing-on-a-probe biosensors reveal association of early SARS-CoV-2 total antibodies and surrogate neutralizing antibodies with mortality in COVID-19 patients [Link] (11/25/20)
  • Test sensitivity is secondary to frequency and turnaround time for COVID-19 screening [Link] (11/25/20)
  • Streamlined inactivation, amplification, and Cas13-based detection of SARS-CoV-2 [Link] (11/20/20)
  • FDA Authorizes First COVID-19 Test for Self-Testing at Home [Link] (11/20/20)
  • Clinical Performances of Three Fully Automated Anti-SARS-CoV-2 Immunoassays Targeting the Nucleocapsid or Spike Proteins [Link] (11/20/20)
  • Detection of SARS-CoV-2 antibodies is insufficient for the diagnosis of active or cured COVID-19 [Link] (11/18/20)
  • Assessment of SARS-CoV-2 RNA Test Results Among Patients Who Recovered From COVID-19 With Prior Negative Results  [Link] (11/18/20)
  • Diagnosis and Tracking of Past SARS-CoV-2 Infection in a Large Study of Vo’, Italy Through T-Cell Receptor Sequencing [Link] (11/18/20)
  • A saliva-based RNA extraction-free workflow integrated with Cas13a for SARS-CoV-2 detection [Link] (11/18/20)
  • Oxford University and PHE confirm high-sensitivity of Lateral Flow Tests following extensive clinical evaluation [Link] (11/13/20)
  • Beckman Coulter introduces new SARS-CoV-2 IgM assay in countries accepting the CE Mark [Link] (11/13/20)
  • EUROIMMUN Launches Quantitative ELISA to Measure SARS-CoV-2 Antibodies Against Viral S1 Protein [Link] (11/13/20)
  • Multiplexed, quantitative serological profiling of COVID-19 from a drop of blood by a point-of-care test  [Link] (11/13/20)
  • FDA Authorizes First Test that Detects Neutralizing Antibodies from Recent or Prior SARS-CoV-2 Infection  [Link] (11/13/20)
  • Association of COVID-19 RT-qPCR test false-negative rate with patient age, sex and time since diagnosis  [Link] (11/13/20)
  • Oxford to trial new COVID-19 test for individuals without symptoms  [Link] (11/13/20)
  • FDA authorizes GenScript cPass SARS-CoV-2 Neutralization Antibody Detection Kit, first serology test that detects neutralizing antibodies from recent or prior SARS-CoV-2 infection [Link] (11/09/20)
  • An optimized digital CRISPR approach, RApid DIgital Crispr Approach (RADICA), enables absolute quantification of viral nucleic acids at a constant temperature in one hour [Link] (11/06/20)
  • Deep learning-based model can detect COVID-19 pneumonia using high-resolution computed tomography with over 95% accuracy [Link] (11/06/20)
  • Stanford researchers combine microfluidics, on-chip electric field control, and CRISPR to create automated device that can identify the coronavirus in just 35 minutes [Link] (11/06/20)
  • SARSeq, saliva analysis by RNA sequencing, can monitor presence of SARS-CoV-2 and other respiratory viruses performed on tens of thousands of samples in parallel [Link] (11/06/20)
  • Use of small nasal strips has a sensitivity of 94% and specificity of 100% for the detection of SARS-CoV-2 in pediatric patients [Link] (11/06/20)
  • Data tested in large cohorts of healthcare workers suggest pooling of 5, 10 and 20 samples as one batch is feasible depending on viral load [Link] (11/04/20)
  • Artificial intelligence model detects asymptomatic Covid-19 infections through cellphone-recorded coughs  [Link] (11/04/20)
  • Agena Bioscience gets FDA Emergency Use Authorization for MassArray coronavirus RT-PCR/MALDI-TOF test that can process thousands of samples in a day [Link] (10/28/20)
  • Ortho Clinical Diagnostics receives CE Mark for its VITROS high-throughput SARS-CoV-2 antigen test, shows 97.8% sensitivity and 99.2% specificity [Link] (10/28/20)
  • DiaSorin high-throughput, rapid antigen SARS-CoV-2 test LIAISON for quantitative detection of SARS-CoV-2 in symptomatic patients receives CE Mark [Link] (10/28/20)
  • FDA updates template for SARS-CoV-2 antigen tests, with recommendations regarding screening asymptomatic individuals and multiplexed tests [Link] (10/28/20)
  • Skin rashes cluster with other COVID-19 symptoms, are predictive of a positive swab test and occur in a significant number of cases, either alone or before other symptoms [Link] (10/28/20)
  • Systematic Parallel Analysis of RNA coupled to Sequencing (C19-SPAR-Seq), a scalable, multiplexed, readily automated NGS platform, can analyze thousands of samples in a single run [Link] (10/20/20)
  • Oxford scientists develop rapid diagnostic test that can detect and identify viruses in less than 5 minutes using machine-learning [Link] (10/16/20)
  • Abbott’s lab-based COVID-19 IgM antibody blood test receives U.S. FDA emergency use authorization and can detect recent or prior infection [Link] (10/16/20)
  • Routine use of point-of-care testing for emergency admissions was associated with a large reduction in time to results and improvements in infection control measures [Link] (10/16/20)
  • FDA grants emergency clearance for GenMark test that detects COVID-19 plus 20 other respiratory ailments [Link] (10/16/20)
  • A convenient, low-cost hemagglutination serology test with a sensitivity of 90% and specificity of 99% can be applied in point-of-care testing [Link] (10/12/20)
  • A nanoparticle-enabled blood test differentiates between samples collected from patients with no or mild symptoms and those with moderate/severe symptoms, with results available in <1 minute [Link] (10/06/20)
  • Inclusion of both SARS-CoV-2 S1 and N in serological testing increases efficiency [Link] (10/06/20)
  • An amplification-free CRISPR-Cas13a-based mobile phone assay for direct detection of SARS-CoV-2 from nasal swab RNA extracts is effective and available at low cost [Link] (10/06/20)
  • Cepheid’s rapid molecular diagnostic multiplex (SARS-CoV-2, Flu, RSV) test receives FDA Emergency Use Authorization [Link] (10/06/20)
  • CRISPR based test, FELUDA, with 96% sensitivity and 98% specificity approved for use in India [Link] (10/06/20)

Select diagnostics kits/assays which have received approval are highlighted below

(*Order by diagnostics kits/assays name A ~ Z)

Product: Advanta Dx SARS-CoV-2 RT-PCR Assay

Date of approval: August 25, 2020 (FDA EUA)

Time: –

Brief Description: Extraction-free saliva-based RT-PCR test

Details: Advanta Dx SARS-CoV-2 RT-PCR Assay, an extraction-free saliva-based test to detect nucleic acid from the SARS‑CoV‑2 virus, designed to be run on the  Fluidigm Biomark HD microfluidics platform. As it is saliva-based, the Advanta Dx SARS-CoV-2 RT-PCR Assay does not require collection via invasive nasopharyngeal swab. The clinical study associated with the EUA submission demonstrated 100 percent agreement between the saliva results from the Advanta Dx SARS-CoV-2 RT-PCR Assay and the results from paired nasopharyngeal samples tested with authorized assays. The company’s microfluidics technology enables processing of more samples per batch than more traditional, microwell plate-based PCR technology. The Biomark HD platform can generate as many as 6,000 test results per day on a single system.

Source Link

Product: BinaxNOW COVID-19 Ag Card

Date of approval: August 26, 2020 (FDA EUA)

Time: 15 min

Brief Description: Ag Card is a rapid, reliable, highly portable, and affordable tool.

Details: Abbott’s BinaxNOW COVID-19 Ag Card is a rapid, reliable, highly portable, and affordable tool for detecting active coronavirus infections at massive scale. Test delivers results in just 15 minutes with no instrumentation, using proven lateral flow technology with demonstrated sensitivity of 97.1% and specificity of 98.5% in clinical study. Abbott will offer a no-charge complementary phone app, which allows people to display their BinaxNOW test results when asked by organizations where people gather, such as workplaces and schools. The company will ship tens of millions of tests in September, ramping to 50 million tests a month at the beginning of October.

Source Link

Product: SalivaDirect

Date of approval: August 15, 2020 (FDA EUA)

Time: Unknown

Brief Description: Saliva Sample Processing without separate nucleic acid extraction.

Details: Yale intends to provide SalivaDirect protocol to interested labs as opensource. SalivaDirect does not require any special type of swab or collection device; a saliva sample can be collected in any sterile container. This test is also unique because it does not require a separate nucleic acid extraction step. This is significant because the extraction kits used for this step in other tests have been prone to shortages in the past. Being able to perform a test without these kits enhances the capacity for increased testing, while reducing the strain on available resources. Additionally, the SalivaDirect methodology has been validated and authorized for use with different combinations of commonly used reagents and instruments, meaning the test could be used broadly in most high-complexity labs.

Source Link

Product: ID NOW COVID-19 assay

Date of approval: March 27, 2020 (FDA EUA)

Brief description: Rapid test targeting COVID-19 RdRp gene (PoC)

Time: Positive results may be detected in as little as 5 minutes and negative results in 13 minutes

Details: ID NOW COVID-19 assay performed on the ID NOW Instrument is a rapid molecular in vitro diagnostic test utilizing an isothermal nucleic acid amplification technology intended for the qualitative detection of nucleic acid from the SARS-CoV-2 viral RNA in direct nasal, nasopharyngeal or throat swabs and nasal, nasopharyngeal or throat swabs eluted in viral transport media from individuals who are suspected of COVID-19 by their healthcare provider.

Source Link

Product: SARS-CoV-2 IgG assay

Date of approval: April 26, 2020 (EUA & CE Mark)

Time: Unknown

Brief Description: Detection of SARS-CoV-2 antibody

Details: The SARS-CoV-2 IgG assay is a chemiluminescent microparticle immunoassay (CMIA) intended for the qualitative detection of IgG antibodies to SARS-CoV-2 in human serum, serum separator tube and plasma (ACD, CPD, CPDA-1, dipotassium EDTA, tripotassium EDTA, lithium heparin, lithium heparin separator tube, sodium citrate, sodium heparin). The SARS-CoV-2 IgG assay is intended for use as an aid in identifying individuals with an adaptive immune response to SARS-CoV-2, indicating recent or prior infection. At this time, it is unknown for how long antibodies persist following infection and if the presence of antibodies confers protective immunity. The SARSCoV-2 IgG assay should not be used to diagnose acute SARS-CoV-2 infection. Testing is limited to laboratories certified under the Clinical Laboratory Improvement Amendments (CLIA) to perform moderate or high complexity test.

Source Link

Product: Alinity m SARS-CoV-2 assay

Date of approval: May 11, 2020 (FDA EUA)

Time: Unknown

Brief Description: Real-time RT-PCR assay to be run on run on the Alinity m system

Details: The Alinity m SARS-CoV-2 assay is a real-time reverse transcriptase (RT) polymerase chain reaction (PCR) test intended for the qualitative detection of nucleic acid from the SARS-CoV-2 in nasal swabs, self-collected at a health care location or collected by a healthcare worker, nasopharyngeal (NP) and oropharyngeal (OP) swabs collected by a healthcare worker or bronchoalveolar lavage fluid (BAL) from patients suspected of COVID-19 by their healthcare provider. Testing is limited to laboratories certified under the CLIA, to perform moderate or high complexity tests.

Source Link

Product: RealTime SARS-C0V-2 assay

Date of approval: March 18, 2020 (EUA)

Details: The Abbott RealTime SARS-C0V-2 assay is an Emergency Use Authorization (EUA) test authorized by the U.S. FDA for use by authorized laboratories, using real-time (RT) polymerase chain reaction (PCR) technology for the qualitative detection of nucleic acids from the SARS-CoV-2 virus and diagnosis of SARS-CoV-2 virus infection from individuals meeting CDC clinical and/or epidemiological testing criteria.

Source Link

Product: LineaCOVID-19 Assay Kit

Date of approval: May 13, 2020 (FDA EUA)

Time: Unknown

Brief Description: RT-PCR based qualitative detection of SARS-CoV-2 RNA

Details: Applied DNA Sciences’ Linea COVID-19 SARS-CoV-2 assay kit is a real-time polymerase chain reaction (RT-PCR) test for the qualitative detection of SAR S-CoV-2 RNA in upper respiratory specimens. The Linea COVID-19 SARS-CoV-2 Assay Kit provides a high-throughput solution to help laboratories address the urgent need for patient testing during the Coronavirus pandemic.

Source Link

Product: iAMP COVID-19 Detection Kit

Date of approval: April 10, 2020 (EUA)

Time: 1.5 h sample to result.

Brief Description: Real-time reverse transcription isothermal amplification test

Details: The test is based on a proprietary isothermal amplification technology termed OMEGA amplification. OMEGA primer sets are designed to specifically detect RNA and later cDNA from the N and ORF-1ab genes of the SARS-CoV-2 virus in nasal, nasopharyngeal and/or oropharyngeal swabs from patients with signs and symptoms of infection who are suspected of COVID-19. The iAMP COVID-19 assay’s key differentiator from current rRT-PCR COVID-19 assays is its ability to detect SARS-CoV-2 RNA directly from samples without prior RNA extraction process.

Source Link

Product: BD Veritor System for Rapid Detection of SARS-CoV-2 (Rapid Antigen Testing)

Date of approval: July 06, 2020 (FDA EUA)

Time: 15 min

Brief Description: Rapid Point-of-Care Antigen Test

Details: FDA granted EUA for a rapid, point-of-care, SARS-CoV-2 diagnostic test for use with its broadly available BD Veritor Plus System. The launch of this new assay that delivers results in 15 minutes on an easy-to-use, highly portable instrument is critical for improving access to COVID-19 diagnostics because it enables real-time results and decision making while the patient is still onsite. BD will begin shipping the new test and expects to ramp-up manufacturing capacity to 2 million tests per week by the end of September.

Source Link

Product: Access SARS-CoV-2 IgG

Date of approval: June 26, 2020 (EUA and CE)

Time: Unknown

Brief Description: Antibodies to SARS-CoV-2 in serum

Details: Qualitative detection of IgG antibodies to SARS-CoV-2 in human serum, serum separator tubes, and plasma (lithium heparin, dipotassium EDTA, tripotassium EDTA, and sodium citrate). Intended for use as an aid in identifying individuals with an adaptive immune response to SARS-CoV-2, indicating recent or prior infection.

Source Link

Product: Real-Time Fluorescent RT-PCR Kit for Detecting SARS-2019-nCoV

Date of approval: April 24, 2020 (EUA)

Brief Description: Taqman RT-PCR for ORF1ab gene

Time: 4 h for 192 samples

Details: On April 24, 2020, the U.S. Food and Drug Administration (FDA) issued an Emergency Use Authorization (EUA) amendment for BGI’s Real-Time Fluorescent RT-PCR Kit for Detecting SARS-CoV-2. The amendment expands the previously issued EUA label to further include the use of automated sample preparation system, additional viral RNA extraction kit and PCR systems for testing a broader range of clinical samples. Specifically, viral RNA extraction can be processed by the kits manufactured by MGI (a subsidiary of BGI Group) or Qiagen. In addition, the highly sensitive SARS-CoV-2 detection test can return results within 4 hours for 192 samples collected from throat (oropharyngeal) swabs, nasopharyngeal swabs, anterior nasal swabs, mid-turbinate nasal swabs, nasal washes, nasal aspirates and bronchoalveolar lavage fluid (BALF) using the MGI automated sample preparation system.

Source Link

Product: BioFire Respiratory Panel 2.1

Date of approval: May 1, 2020 (EUA)

Time: Unknown

Brief Description: Multiplex RT PCR for identification of several viruses including COVID-19

Details: BioFire Respiratory Panel 2.1 is a multiplexed nucleic acid test intended for the simultaneous qualitative detection and differentiation of nucleic acids from multiple respiratory viral and bacterial organisms, including nucleic acid from the SARS-CoV-2 virus, in nasopharyngeal swabs (NPS) obtained from individuals suspected of COVID-19 by their healthcare provider.

Source Link

Product: 2019-nCoV IgG/IgM Antibody Detection Kit (Colloidal Gold)

Date of approval: April 6, 2020 (CE)

Brief Description: IgG/IgM Antibody Detection Kit

Time: 10 min.

Details: Simultaneous detection of SARS-CoV-2 specific IgM and IgG antibodies: The 2019-nCov IgG/IgM Rapid Test Device is a rapid chromatographic immunoassay for the qualitative detection of IgG & IgM antibody of Coronavirus in human venous whole blood, serum or plasma.

Source Link

Product: SARS-COV-2 R-GENE

Date of approval: May 6, 2020 (EUA)

Time: 4-5 h

Brief Description: Real-time PCR kit for the detection of SARS-COV-2

Details: The SARS-COV-2 R-GENE kit is a molecular detection kit, using real-time PCR after viral nucleic acids extraction. Assay includes all necessary reagents optimized to detect SARS-COV-2 for in vitro diagnostic use. Two triplex PCR for reliable diagnosis even if the virus mutates – PCR 1: SARS-COV-2 N gene (FAM) / Internal Control (HEX) / SARS-COV-2 RdRp gene (CY5) and PCR 2: SARBECOVIRUS E gene (FAM) / Internal Control (HEX) / Cellular Control (CY5)

Source Link

Product: Bio-Rad SARS-CoV-2 ddPCR Test & Platelia SARS-CoV-2 Total Ab assay

Date of approval: May 1, 2020 (EUA)

Time: Unknown

Brief Description: Quantitative Droplet Digital PCR & Qualitative detection of anti COVID-19 antibodies, based on immunoassay

Details:

Bio-Rad SARS-CoV-2 ddPCR Test: Qualitative detection of nucleic acid from SARS-CoV-2 innasopharyngeal, anterior nasal and mid-turbinate nasal swabspecimens as well as nasopharyngeal wash/aspirate and nasalaspirate specimens collected from individuals suspected of COVID-19 by their healthcare provider. Emergency use of thistest is limited to authorized laboratories.

Platelia SARS-CoV-2 Total Ab assay: Qualitative detection of total antibodies (including IgM/IgA/IgG) to SARS-CoV-2 in human serum and plasma (EDTA). Intendedfor use as an aid in identifying individuals with an adaptiveimmune response to SARS-CoV-2, indicating recent or priorinfection. Emergency use of this test is limited to authorizedlaboratories.

Source Link

Product: COVID-19 RT-PCR Peptide Nucleic Acid (PNA) kit

Date of approval: June 30, 2020 (EUA)

Time: Unknown

Brief Description: RT-qPCR PNA KIT

Details: The COVID-19 RT-qPCR PNA KIT is developed with reusable fluorescence hybridization probe real-time PCR technique using Peptide Nucleic Acid (PNA), sort of artificial nucleic acid which has more higher binding ability to its complement sequence DNA than which of DNA one, to in vitro reverse transcription of SARS-CoV-2 (also known as SARS-2019-nCoV) RNA followed with cDNA amplification and detection. The kit targets three specific genomic regions of SARS-CoV-2, those are RNA dependent RNA Polymerase (RdRP) gene , Nucleocapsid (N).

Source Link

Product: CRSP SARS-CoV-2 Real-time Reverse Transcriptase (RT)-PCR Diagnostic Assay

Date of approval: July 8, 2020 (FDA EUA)

Time: NA

Brief Description: RT-PCR based qualitative detection of SARS-CoV-2 RNA

Details: The CRSP SARS-CoV-2 Real-time Reverse Transcriptase (RT)-PCR Diagnostic Assay is a real-time RT-PCR test intended for the qualitative detection of nucleic acid from the SARS-CoV-2 in nasopharyngeal and oropharyngeal swabs collected from individuals who may have contracted the virus. Testing is limited to the Clinical Research Sequencing Platform at the Broad Institute which is certified under the CLIA, to perform high complexity tests.

Source Link

Product: qSARS-CoV-2 IgG/IgM Rapid Test

Date of approval: April 1, 2020 (EUA)

Brief Description: Lateral flow immunoassay for IgM and IgG antibodies

Time: 15 to 20 min.

Details: The Cellex qSARS-CoV-2 IgG/IgM Rapid Test is a lateral flow immunoassay intended for the qualitative detection and differentiation of IgM and IgG antibodies to SARS-CoV-2 in serum, plasma (EDTA, citrate) or venipuncture whole blood specimens from patients suspected of COVID-19 infection by a healthcare provider.

Source Link

Product: CDC Influenza SARS-CoV-2 (Flu SC2) Multiplex Assay

Date of approval: July 02, 2020

Time: Unknown

Brief Description: RT-PCR based multiplex assay

Details: The CDC Influenza SARS-CoV-2 (Flu SC2) Multiplex Assay is a real-time reverse-transcriptase polymerase chain reaction (RT-PCR) test that detects and differentiates RNA from SARS-CoV-2, influenza A virus, and influenza B virus in upper or lower respiratory specimens. The assay provides a sensitive, nucleic-acid-based diagnostic tool for evaluation of specimens from patients in the acute phase of infection.

Source Link

Product: SARS-CoV-2 RT-PCR Test

Date of approval: July 01, 2020

Time: Unknown

Brief Description: RT-PCR based SARS-CoV-2 RNA detection kit

Details: CENTOGENE’S SARS-CoV-2 RT-PCR test is a real-time test based on the reverse transcription polymerase chain reaction (RT-PCR) for the qualitative detection of SARS-CoV-2, the underlying virus causing COVID-19. It is intended to be used with samples of the upper respiratory tract (oropharyngeal swabs) collected from individuals suspected by their healthcare provider to have COVID-19, belonging to a risk cohort, or having been in contact with a confirmed COVID-19 patient. The test is intended for use by qualified laboratory personnel to be performed in CENTOGENE’s CLIA certified high-complexity laboratories in Germany.

Source Link

Product: Xpert Xpress SARS-CoV-2 test

Brief Description: Rapid, near-patient RT-PCR test

Date of approval: March 20, 2020 (EUA)

Time: 30 min.

Details: Cepheid has developed an automated molecular test for the qualitative detection of SARS-CoV-2, the virus that causes COVID-19. The test leverages the design principles of our current Xpert Xpress Flu/RSV cartridge technology, in which multiple regions of the viral genome are targeted. The test can provide rapid detection of the current pandemic coronavirus SARS-CoV-2 in as soon as 30 minutes for positive results with less than a minute of hands on time to prepare the sample.

Source Link

Product: Logix Smart Coronavirus Disease 2019 (COVID-19) Kit

Date of approval: April 3, 2020 (EUA)

Brief Description: Single step real-time RT-PCR

Time: 63-90 min., depending on PCR equipment.

Details: The Logix Smart Coronavirus Disease 2019 (COVID-19) Test kit is an in vitro diagnostic test that uses our patented CoPrimer technology for the qualitative detection of the RNA from SARS-CoV-2 coronavirus (COVID-19). The test operates using a single step real-time reverse transcriptase polymerase chain reaction (RT-PCR) process in lower respiratory tract fluids (e.g. bronchoalveolar lavage, sputum, tracheal aspirate), and upper respiratory tract fluids (e.g. nasopharyngeal and oropharyngeal swabs) from patients who meet the clinical criteria. The test is available to laboratories certified under the CLIA.

Source Link

Product: LIAISON SARS-CoV-2 SOLUTIONS

Date of approval: April 24, 2020 (EUA)

Time: Unknown

Brief Description: SARS-CoV-2 IgM and SARS-CoV-2 S1/S2 IgG

Details: The testing solutions are based on two results from a single sample to determine both antibodies results. The selection of Spike protein antigens for both assays, recognized to be the most likely target of future COVID-19 vaccines and for IgG neutralizing antibodies. High sensitivity and specificity to ensure accurate results along the infection window. The use of IgG and IgM in combination can aid to shorten the diagnostic window improving the detection of seroconversion up to day 15 from PCR positivity.

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Product: Anti-SARS-CoV-2 ELISA (IgG)

Date of approval: May 4, 2020 (EUA, CE)

Time: Unknown

Brief Description: Anti-SARS-CoV-2 ELISA (IgG)

Details: ELISA test Qualitative detection of IgG antibodies against SARS-CoV-2 in human serum and plasma (K+-EDTA, Li+-heparin, Na+-citrate). Intended for use as an aid in identifying individuals with an adaptive immune response to SARS-CoV-2, indicating recent or prior infection.

Source Link

Product: EURORealTime SARS-CoV-2

Date of approval: June 8, 2020 (EUA, CE)

Time: Unknown

Brief Description: SARS-CoV-2 RT-PCR test

Details: Qualitative detection of nucleic acid from SARS-CoV-2 in upper respiratory specimens (such as nasal, nasopharyngeal, midturbinate and oropharyngeal swabs) and bronchioalveolar lavage (BAL) from individuals suspected of COVID-19 by their healthcare provider.

Source Link

Product: Illumina COVIDSeq Test

Date of approval: June 9, 2020

Time: 12 h

Brief Description: SARS-CoV-2 RT-PCR test

Details: The Illumina COVIDSeq Test is the first NGS test approved for use under the U.S. Food and Drug Administration’s Emergency Use Authorization (EUA). This amplicon-based NGS test includes 2019-nCoV primer and probe sets designed to detect RNA from the SARS-CoV-2 virus in nasopharyngeal, oropharyngeal, and mid-turbinate nasal swabs from patients with signs and symptoms of infection who are suspected of COVID-19.

Source Link

Product: SCoV-2 Detect IgM ELISA & SCoV-2 Detect IgG ELISA

Date of approval: June 30, 2020 (EUA) for IgM & June 10, 2020 (EUA) for IgG

Time: Unknown

Brief Description: ELISA that specifically detects IgM antibodies and IgG antibodies to SARS-CoV-2

Details:

The SCoV-2 Detect IgM ELISA is an in vitro diagnostic test for the qualitative detection of IgM antibodies to SARS-CoV-2 in human serum. The test is intended for use as an aid in identifying individuals with an adaptive immune response to SARS-CoV-2, indicating recent or prior infection. At this time, it is unknown for how long antibodies persist following infection and if the presence of antibodies confers protective immunity. The SCoV-2 Detect IgM ELISA should be used to diagnose acute SARS-CoV-2 infection.
The SCoV-2 Detect IgG ELISA kit is an in vitro diagnostic test for the qualitative detection of IgG antibodies to SARS-CoV-2 in human serum. The test is intended as an aid in identifying individuals with an adaptive immune response to SARS-CoV-2, indicating recent or prior infection. At this time, it is unknown for how long antibodies persist following infection and if the presence of antibodies confers protective immunity. The SCoV-2 Detect IgG ELISA should not be used to diagnose acute SARS-CoV-2 infection.

Source Link: IgM assay, IgG assay

Product: COVID-19 RT-PCR Test

Date of approval: July 24, 2020 (FDA EUA)

Time: Unknown

Brief Description: First Diagnostic Test for Screening of People Without Known or Suspected COVID-19 Infection; Allows pooled testing.

Details: U.S. Food and Drug Administration reissued the LabCorp COVID-19 RT-PCR Test emergency use authorization (EUA) to include two new indications for use: testing for people who do not have COVID-19 symptoms or who have no reason to suspect COVID-19 infection, and to allow pooled sample testing.

Source Link

Product: xMAP SARS-CoV-2 Multi-Antigen IgG Assay

Date of approval: July 16, 2020 (FDA EUA)

Time: Up to 96 samples per run in less than 3 h

Brief Description: SARS-CoV-2 antibody assay

Details: Detects IgG antibodies against 3 SARS-CoV-2 antigens, providing comprehensive results: S1 subunit of the spike protein, RBD of the spike protein, Nucleocapsid protein. It is designed for use with human serum and plasma samples, eliminating the need to implement additional collection protocols.

Source Link

Product: ARIES SARS-CoV-2 Assay

Date of approval: April 3, 2020 (EUA)

Time: Minimal hands-on time and an automated workflow delivers results in about 2 h

Brief Description: Exonuclease-sensitive probes for the ORF1ab and N viral genes provide superior specificity.

Details: This product is a qualitative test for the detection of SARS-CoV-2 nucleic acids in nasopharyngeal swab specimens from individuals suspected of COVID-19 by their healthcare provider. The SARS-CoV-2 nucleic acid is detectable in nasopharyngeal swab specimens during the acute phase of infection. Positive results are indicative of the presence of SARS-CoV-2 nucleic acid; clinical correlation with patient history and other diagnostic information is necessary to determine patient infection status. Positive results do not rule out bacterial infection or co-infection with other viruses.

Source Link

Product: NxTAG CoV Extended Panel Assay

Date of approval: March 27, 2020 (EUA)

Time: 96 samples in approximately 4 h.

Brief Details: SARS-CoV-2 detection using three viral genes (ORF1ab, E gene, and N gene)

Details: NxTAG CoV Extended Panel Assay for use on Luminex MAGPIX instrument is a RT-PCR test intended for the qualitative detection of nucleic acid from the SARS-CoV-2 in nasopharyngeal swab specimens from individuals suspected of COVID-19 by their healthcare provider.

Source Link

Product: Accula SARS-Cov-2 Test

Brief Description: Rapid point-of-care PCR test

Date of approval: March 23, 2020 (FDA EUA)

Time: 30 min.

Details: Mesa Biotech has developed a qualitative, visually read test utilizing polymerase chain reaction (PCR) technology to detect SARS-CoV-2, the virus responsible for COVID-19. Using throat and nasal swabs, results are available in 30 minutes, based on the principles of Mesa’s commercially available Accula Influenza and RSV tests.

Source Link

Product: COVID-19 ELISA IgG Antibody Test

Date of approval: April 15, 2020 (EUA)

Brief Description: ELISA test IgG Antibody Test

Details: The COVID-19 ELISA IgG Antibody Test consists of two serial direct assays (ELISA) for the qualitative detection of human IgG antibodies in serum and plasma specimens collected from individuals suspected of prior infection with the virus that causes COVID-19 by their healthcare provider. An initial ELISA is performed against recombinant Receptor Binding Domain of SARS-CoV-2 in serum and plasma, followed for positive specimen by a confirmatory ELISA against full length SARS-CoV-2 Spike protein in serum and plasma. The COVID-19 ELISA IgG Antibody Test detects IgG antibodies as indicative of an immune response to SARS-CoV-2 in patients suspected of previous SARS-CoV-2 infection, or for the detection of IgG seroconversion in patients following known recent SARS-CoV-2 infection. The test is an aid in the diagnosis of patients with suspected of prior COVID-19 in conjunction with clinical presentation and the results of other laboratory tests. Results from the COVID-19 ELISA IgG Antibody Test should not be used as the sole basis for diagnosis and should not be used for the diagnosis of patients with acute COVID-19 infection. Testing is limited to the Mount Sinai Laboratory (MSL).

Source Link

Product: OPTI SARS-CoV-2 RT PCR Test

Date of approval: May 6, 2020

Time: Unknown

Brief Description: Real-time RT-PCR COVID-19 detection kit

Details: OPTI SARS-CoV-2 RT PCR Test is a qualitative test for the detection of nucleic acid from SARS-CoV-2 in upper and lower respiratory specimens (such as nasal, nasopharyngeal, oropharyngeal swabs, sputum, lower respiratory tract aspirates, bronchoalveolar lavage, and nasopharyngeal wash/aspirate or nasal aspirate) from patients suspected of COVID-19 by their health care provider. The SARSCoV-2 nucleic acid is generally detectable in upper and lower respiratory specimens during the acute phase of infection. Positive results are indicative of the presence of SARS-CoV-2 nucleic acid; clinical correlation with patient history and other diagnostic information is necessary to determine patient infection status. Positive results do not rule out bacterial infection or coinfection with other viruses.

Source Link

Product: VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total Reagent Pack and Calibrators.

Date of approval: April 14, 2020 (EUA)

Time: Unknown

Brief Description: VITROS Anti-SARS-CoV-2 Total and IgG tests

Details: This test is one of the first high-throughput, automated COVID-19 antibody tests to be granted Emergency Use Authorization. Total antibody test detects all antibodies – IgM, IgA, and IgG and helps identify current or past exposure to SARS-CoV-2 whereas the IgG test detects the IgG antibody and helps identify an adaptive immune response.

Source Link

Product: VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total Reagent Pack

Date of approval: April 14, 2020

Time: 48 min

Details: The VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total Reagent Pack test when used in combination with the VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total Calibrator is for the qualitative measurement of total antibody (including IgG and IgM) to SARS-CoV-2 in human serum and plasma (K2 EDTA) samples from patients suspected of COVID-19 by a healthcare provider, using VITROS ECi/ECiQ/3600 Immunodiagnostic Systems and the VITROS 5600/XT 7600 Integrated Systems. The VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total Reagent Pack test is an aid in the diagnosis of patients with suspected SARS-CoV-2 infection in conjunction with clinical presentation and the results of other laboratory tests. Results from the VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total Reagent Pack test should not be used as the sole basis for diagnosis. Testing is limited to laboratories certified under the CLIA, to perform moderate and high complexity tests .

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Product: GeneFinder COVID-19 Plus RealAmp Kit

Date of approval: April 18, 2020 (FDA EUA, CE)

Brief Description: One step RT-PCR Kit

Time: 120 min

Details: GeneFinder COVID-19 Plus RealAmp Kit is the One-Step Reverse Transcription Real-Time PCR Kit designed to detect Novel Corona virus (COVID-19) qualitatively through Reverse Transcription reaction and Real-Time Polymerase Chain Reaction. It provides in about 120 minutes, detection for COIVD-19 in a single tube.

Source Link

Product: QIAstat-Dx Respiratory SARS-CoV-2 Panel

Date of approval: March 30, 2020 (EUA)

Time: Less than one minute for sample preparation and delivers results in about one hour.

Brief Description: A multiplexed nucleic acid real-time PCR test

Details: The QIAstat-Dx test kit can differentiate the SARS-CoV-2 coronavirus from 20 other respiratory infections in patients who may have similar symptoms in a single testing run of about one hour. It is a multiplexed nucleic acid test that evaluates samples such as nasopharyngeal swabs obtained from individuals suspected of respiratory tract infections. This new panel includes assays targeting two genes used to detect SARS-CoV-2, the pathogen behind the disease.

Source Link

Product: Quest SARS-CoV-2 rRT-PCR

Date of approval: July 18, 2020 (FDA EUA)

Time: Up to 96 samples per run in less than 3 h

Brief Description: The Quest test is the first COVID-19 diagnostic test to be authorized for use with pooled samples.

Details: This test is for the qualitative detection of nucleic acid from the SARS-CoV-2 in pooled samples containing up to four individual upper respiratory swab specimens (nasopharyngeal, mid-turbinate, anterior nares or oropharyngeal swabs) that are collected under observation using individual vials containing transport media from individuals suspected of COVID19 by their healthcare provider.

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Product: Sofia 2 SARS Antigen FIA

Date of approval: May 8, 2020

Time: 15 min

Brief Description: Lateral flow (strip) test for COVID-19 nucleocapsid protein

Details: Sofia 2 SARS Antigen FIA is a lateral flow immunofluorescent sandwich assay that is used with the Sofia 2 Instrument intended for the qualitative detection of the nucleocapsid protein antigen from SARSCoV-2 in nasopharyngeal (NP) and nasal (NS) swab specimens directly or after the swabs have been added to viral transport media from individuals who are suspected of COVID-19 by their healthcare provider. The SARS-CoV-2 nucleocapsid protein antigen is generally detectable in respiratory specimens during the acute phase of infection. Positive results are indicative of the presence of SARS-CoV-2 nucleocapsid protein antigen, but clinical correlation with patient history and other diagnostic information is necessary to determine infection status. Positive results do not rule out bacterial infection or co-infection with other viruses. Negative results should be treated as presumptive and confirmed with a molecular assay, if necessary for patient management.

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Product: Lyra Direct SARS-CoV-2 Assay

Date of approval: May 19, 2020

Time: Unknown

Brief Description: RT-PCR based SARS-CoV-2 RNA detection kit

Details: Lyra Direct SARS-CoV-2 Assay is a qualitative test for the detection of nucleic acid from SARS-CoV-2 in nasal (NS), nasopharyngeal (NP), or oropharyngeal (OP) direct swab specimens from individuals suspected of COVID-19 by their healthcare provider. The SARS-CoV-2 nucleic acid is generally detectable in upper respiratory specimens during the acute phase of infection. Positive results are indicative of the presence of SARS-CoV-2 nucleic acid; clinical correlation with patient history and other diagnostic information is necessary to determine patient infection status. Positive results do not rule out bacterial infection or co-infection with other viruses.

Source Link

Product: Elecsys Anti-SARS-CoV-2

Date of approval: May 2, 2020

Time: Unknown

Brief Description: Immunoassay to detect anti-COVID-19 antibodies

Details: Elecsys Anti-SARS-CoV-2 is a qualitative test for the detection of antibodies against SARS-CoV-2 in human serum or plasma (Heparin or EDTA). The product is intended for use as an aid in identifying individuals with an adaptive immune response to SARS-CoV-2, indicating recent or prior infection

Source Link

Product: cobas SARS-CoV-2 test

Date of approval: March 12, 2020 (EUA), CE-IVD

Time: 96 results in about 3.5 h and a total of 384 results for the cobas 6800 System and 1056 results for the cobas 8800 System in 8 h.

Brief Description: RT-PCR for qualitative detection of SARS-CoV-2

Details: The tests are for use on the automated cobas 6800/8800 Systems under Emergency Use Authorization. Test is a single-well dual target assay, which includes both specific detection of SARS-CoV-2 and pan-sarbecovirus detection for the sarbecovirus subgenus family that includes SARS-CoV-2. The assay has a full-process negative control, positive control and internal control. Results are for the detection of SARS-CoV-2 RNA that are detectable in nasal, nasopharyngeal, and oropharyngeal swab samples during infection.

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Product: Rutgers Clinical Genomics Laboratory TaqPath SARS-CoV-2 Assay

Date of approval: May 7, 2020

Time: Unknown

Brief Description: RT-PCR kit

Details: Rutgers Clinical Genomics Laboratory TaqPath SARS-CoV-2 Assay is a qualitative test for the detection of nucleic acid from SARS-CoV-2 in in oropharyngeal (throat) swab, nasopharyngeal swab, anterior nasal swab, mid-turbinate nasal swab, and bronchoalveolar lavage (BAL) fluid from individuals suspected of COVID-19 by their healthcare provider.

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Product: Novel Coronavirus (2019-nCoV) Nucleic Acid Diagnostic Kit (PCR-Fluorescence Probing)

Date of approval: May 4, 2020 (EUA)

Time: Unknown

Brief Description: Real time RT-PCR using approved real-time PCR instrument

Details: Novel Coronavirus (2019-nCoV) Nucleic Acid Diagnostic Kit (PCR-Fluorescence Probing is a qualitative test for the detection of nucleic acid from SARS-CoV-2 in nasopharyngeal swabs, oropharyngeal (throat) swabs, anterior nasal swabs, mid-turbinate swabs, nasal washes, and nasal aspirates from individuals suspected of COVID-19 by their healthcare provider. The SARS-CoV-2 nucleic acid is generally detectable in respiratory specimens during the acute phase of infection. Positive results are indicative of the presence of SARS-CoV-2 nucleic acid; clinical correlation with patient history and other diagnostic information is necessary to determine patient infection status. Positive results do not rule out bacterial infection or co-infection with other viruses.

Source Link

Product: Allplex 2019-nCoV Assay

Date of approval: April 21, 2020 (EUA)

Time: 1 h 50 min

Brief Description: Multiplex real-time RT-PCR-based detection system

Details: Allplex test kit is a qualitative test for the detection of nucleic acid from SARS-CoV-2 in human nasopharyngeal swab, oropharyngeal swab, anterior nasal swab, mid-turbinate and sputum specimens from individuals who are suspected of COVID-19 by their health care provider. Detection and identification of target genes (E gene, RdRP gene, N gene) specific for COVID-19 in a single tube.

Source Link

Product: Dimension Vista SARS-CoV-2 Total antibody assay (COV2T)

Date of approval: June 8, 2020 (EUA)

Time: Unknown

Brief Description: Total Antibody, CLIA

Details: The COV2T assay detects both IgM and longer-lasting IgG antibodies with high sensitivity of recent and prior infection. This allows for identification of patients who have developed an adaptive immune response, which indicates recent infection or prior exposure.

Source Link

Product: Sherlock CRISPR SARS-CoV-2 Kit

Date of approval: May 6, 2020

Time: Unknown

Brief Description: The assay is comprised of two steps. Step one is RT-LAMP where targeted SARS-CoV-2 genomic RNA is reverse transcribed to DNA then amplified by a strand-displacing DNA polymerase. Step two transcribes the amplified DNA to activate collateral cleavage activity of a CRISPR complex programmed to the target RNA sequence.

Details: Based on the SHERLOCK method, which stands for Specific High-sensitivity Enzymatic Reporter unLOCKing, the kit works by programming a CRISPR molecule to detect the presence of a specific genetic signature – in this case, the genetic signature for SARS-CoV-2 – in a nasal swab, nasopharyngeal swab, oropharyngeal swab or bronchoalveolar lavage (BAL) specimen. When the signature is found, the CRISPR enzyme is activated and releases a detectable signal. In addition to SHERLOCK, the company is also developing its INSPECTR platform to create an instrument-free, handheld test – similar to that of an at-home pregnancy test – that utilizes Sherlock Biosciences’ Synthetic Biology platform to provide rapid detection of a genetic match of the SARS-CoV-2 virus.

Source Link

Product: Stanford SARS-CoV-2 assay

Date of approval: April 8, 2020 (EUA)

Time: 2-3 days

Details: The Stanford Clinical Virology Laboratory was one of the first academic medical labs in the country to develop and administer a diagnostic test for the COVID-19 virus. Since starting to use the test in early March, more than 12,000 have been conducted on samples collected from people with symptoms of COVID-19 or with a known exposure to someone with the disease. Of these, about 9% have tested positive. The laboratory currently performs as many as 2,000 tests per day from samples collected at several Bay Area locations.

Source Link

Product: TaqPath COVID-19 Combo Kit.

Date of approval: March 13, 2020 (FDA EUA).

Brief Description: Multiplex real-time PCR detection of RNA from the SARS-CoV-2

Time: 94 patient specimens in under 3 hours.

Details: The TaqPath COVID-19 Combo Kit consists of both the TaqPath RT-PCR COVID-19 Kit and the TaqPath COVID-19 Control Kit. The kit can be used by clinical and public health laboratories to quickly evaluate up to 94 patient specimens in under 3 hours. The kit is approved for use with RNA extracted from nasopharyngeal swabs, nasopharyngeal aspirate (nasal aspirate), and bronchoalveolar lavage (BAL) from patients at risk of exposure to the SARS-CoV-2 virus or with signs and symptoms of COVID-19. Testing is limited to laboratories certified under the CLIA.

Source Link

Product: New York SARS-CoV Microsphere Immunoassay for Antibody Detection

Date of approval: April 30, 2020 (EUA)

Time: Unknown

Brief Description: Microsphere Immunoassay for Antibody Detection (IgG, IgM, IgA).

Details: Qualitative detection of total antibody (IgG, IgM, and IgA) to SARS-CoV-2 in human serum. Intended for use as an aid in identifying individuals who may have high levels of SARS-CoV-2-reactive antibodies in their blood that reflect an adaptive immune response to SARS-CoV-2 indicating recent or prior infection. Emergency use of this test is limited to Wadsworth Center, New York State Department of Health, which is certified under the CLIA to perform high complexity tests.

Source Link

Product: Quick SARS-CoV-2rRT-PCR Kit

Date of approval: May 7, 2020

Time: Unknown

Brief Description: RT-PCR COVID-19 detection kit

Details: Quick SARS-CoV-2rRT-PCR Kit is a qualitative test for the detection of nucleic acid from SARS-CoV-2 in upper respiratory specimens (such as nasal, nasopharyngeal, mid-turbinate or oropharyngeal swabs), and lower respiratory specimens (such as sputum, tracheal aspirates, and bronchoalveolar lavage) from patients suspected of COVID-19 by their healthcare provider. The SARS-CoV-2 nucleic acid is generally detectable in respiratory specimens during the acute phase of infection. Positive results are indicative of the presence of SARS-CoV-2 nucleic acid; clinical correlation with patient history and other diagnostic information is necessary to determine patient infection status. Positive results do not rule out bacterial infection or co-infection with other viruses

Source Link

Updated: 25 November, 2020.

Following is the list of all SARS-CoV-2 tests commercially available or in development for the diagnosis of COVID-19 collated by the Foundation for Innovative New Diagnostics (FIND), which is information directly submitted by test suppliers or obtained from publicly available sources.

An Overview of Coronavirus (COVID-19) Vaccine Candidates

Over the past 18 years, Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome (MERS), and now COVID-19 (SARS-CoV-2) have caused unimaginable distress, mortality, morbidity, social disturbances, and economic disruptions [1]. To mitigate the consequences of COVID-19 and to protect from future pandemics, vaccines are urgently needed. Since the pandemic started, scientists worldwide are evaluating different approaches at unprecedented speed with novel paradigms and accelerated development to trigger the immune system to produce effective neutralizing antibodies and enough T-cells that can fight COVID-19, in hopes of inducing the kind of responses that maybe associated with protection and minimal adverse events. The World Health Organization (WHO) maintains a working document that includes most of the vaccines in development. As of October 27, 2020, there were 44 candidate vaccines in clinical testing and 153 candidate vaccines in preclinical evaluation as per the continually updated published draft vaccine landscape by WHO.

Figure 1. An overview of different approaches to vaccine development. Image for illustration purpose only.

Fig. 1 shows at least eight different approaches that have been explored for the development of a vaccine. These include Whole virus vaccines (Weakened or Inactivated form), Viral-vector vaccines (Replicating or Non-replicating), Genetic forms (RNA, DNA), Protein-based vaccines (Subunit or Virus-like Particles). In addition, pre-existing vaccines (e. g. MMR, Poliovirus, or Tuberculosis) are being explored as well for the possibility that these might confer protection against the SARS-CoV-2 virus.

Vaccine Development Timelines

Steps and timelines for traditional and pandemic vaccine development are shown in Fig. 2. The traditional vaccine testing process begins with the Preclinical trials (in labs, and then in animals if it shows potential) followed by  the Phase 1 safety trials (20-100 healthy volunteers), the expanded Phase 2 trials (several hundred enrolled for observing common short-term side effects and dosing responses), and then Phase 3 efficacy trials (hundreds or thousands of volunteers). Vaccinated people are compared with people who have received a placebo or another vaccine so researchers can learn more about the test vaccine’s safety and effectiveness and identify common side effects.  Once a vaccine is successfully passed these requirements, the approval process is followed (CDC; FDA). A decade or longer is more typical for the completion of a successful candidate.

However, in a pandemic situation, a vaccine may receive Emergency Use Authorization (EUA) before getting any kind of formal approval, Phases 2 and 3 may be combined to shorten the time for development, and the Human challenge trials (controlled human infection model) can be skipped. The WHO Research Ethics Review Committee (ERC) was split over whether COVID-19 Human challenge trials should be performed in the absence of a rescue treatment. The current speed with which vaccines are being developed is remarkable, from the first deciphering of the SARS-CoV-2 genome published on 11 January 2020 through Phase 3 trials in 6 months, as compared with a typical timeline of 2 to 10 years. It should be noted that several companies have already pursued large scale manufacturing of vaccines before establishing the vaccine safety, efficacy and/or receiving the final regulatory approval.

Figure 2. Timelines for traditional and pandemic models of vaccine development.

As of October 27, 2020, as per the WHO, there were 153 vaccine programs in preclinical stages, and 21, 13, and 10 vaccines in Phase 1, Phase 2 (Phase 1/2) and Phase 3, respectively. In an unprecedented move, the vaccine candidate from CanSino Biologics was approved for limited use on June 25. CanSino has been conducting its Phase 3 trials in several countries, including Saudi Arabia and Russia. On August 11, the vaccine candidate Sputnik V from Gamaleya Research Institute, part of Russia’s Ministry of Health, was conditionally approved before Phase 3 trials. Another candidate from Russia, EpiVacCorona from the Vector Institute was granted regulatory approval. On September 14, the U.A.E. government, following intermediate results from ongoing trials, gave emergency approval for Sinopharm’s vaccine to be used on health care workers as a priority. Chinese company Sinovac Biotech is testing their candidate in Phase 3 after receiving the emergency approval for limited use in July (Source: Vaccine tracker).

Current Status

As of October 27, 2020, the global COVID-19 vaccine landscape included 197 vaccine candidates (Fig. 3); with 153 currently at exploratory or preclinical stages and 44 moving into clinical stages. Several advanced candidates have moved ahead into clinical development, including mRNA-1273 from ModernaBNT162b1 from Pfizer, ChAdOx1 nCoV-19 from University of Oxford and AstraZeneca, Ad5-nCoV from CanSino Biologicals, and CoronaVac from Sinovac Biotech.

Figure 3. Pipeline of Vaccine candidates by technology platform and development stages (data source: WHO)

One example, the mRNA-1273 vaccine candidate manufactured by Moderna, is a novel lipid nanoparticle (LNP)-encapsulated mRNA-based vaccine that encodes for a full-length, prefusion stabilized Spike (S) protein of SARS-CoV-2. The purpose of this design was to stimulate neutralizing antibodies directed at a portion of the S protein, which the virus uses to bind to human receptor and enter human cells [2]. Based on the results of the Phase 1 study, the 100 ug dose level was chosen as the optimal dose level to maximize the immune response while minimizing adverse reactions. Phase 1 trial assessing mRNA-1273 demonstrated that the two-dose vaccine series did not cause severe adverse events and could elicit neutralization and Th1-biased CD4+ T-cell responses [2, 3].  A large Phase 3 efficacy trial, the COVE study, was designed in collaboration with the FDA and NIH to evaluate Americans at the highest risk of severe COVID-19 disease. Moderna on October 22 announced that it has completed enrollment of 30,000 participants for the Phase 3 COVE study of mRNA-1273 [16].

The leading candidates (Table 1), currently undergoing Phase 3 evaluations, are based on platforms that either utilize non-replicating viral vectors, inactivated virus, or protein subunits. These primed a better targeted immune response against SARS-CoV-2 infection. According to early results, these candidates have illustrated [1, 17] the ability to generate a substantial T-cell response against SARS-CoV-2 and [2] the ability to increase the levels of neutralizing antibodies that were effective in binding the S-protein of COVID-19 receptor binding domain [2-10].

Table 1. The characteristics of clinical-phase vaccine candidates (October 27, 2020).

Repurposed (Pre-existing) Vaccines

Given the imperative for scale and speed, epidemiological investigations have suggested a strong correlation among countries with universal vaccination policies and the severity of COVID-19. Findings suggested that countries with universal vaccination policies against Bacillus Calmette-Guerin  (BCG, Tuberculosis) and/or against MMR (Measles, Mumps and Rubella) showed a significant reduction of mortality and infection rates [11-13]. Authors suggest that such pre-existing vaccines may boost an individual’s immune response, reduce the severity of COVID-19, and alleviate the symptoms associated with COVID-19. Multiple such studies have revealed interesting associations with COVID-19 severity and vaccination coverage in the population [13, 14]. Despite the initiation of clinical trials (NCT04327206; NCT04357028), the WHO does not recommend such re-purposed vaccines until scientific evidence is provided. As cautioned by the WHO and while still in the middle of this pandemic, COVID-19 cases and deaths continue to increase over time in some BCG-using countries (e.g. Brazil, India, and Mexico) [Johns Hopkins, 15].

Finally, as the world awaits the vaccine as a salvation, strong coalition between developers, researchers, politicians, regulators, and funders will be needed to ensure that the approved vaccine candidate can be manufactured in large quantities and be supplied impartially to all impacted areas. The FDA has released guidelines for the development and licensure of SARS-CoV-2 vaccines, which also states that an efficacy of at least 50% will be required [18].

Regular updates and details on promising vaccine candidates are outlined in our “Highlights” tab (Dashboard).

Prepared by: Fuad Odeh & Sudheer Krishna. Updated : 27 October, 2020.

References

  1. COVID-19, SARS and MERS: are they closely related? Petrosilo et al. (2020), Clinical Microbiology and Infection: https://doi.org/10.1016/j.cmi.2020.03.026
  2. SARS-CoV-2 mRNA Vaccine Development Enabled by Prototype Pathogen Preparedness, K. S. Corbett, bioRxiv (2020): https://doi.org/10.1101/2020.06.11.145920
  3. An mRNA Vaccine against SARS-CoV-2 — Preliminary Report, Jackson et al., (2020) The New England Journal of Medicine (2020): DOI: 10.1056/NEJMoa2022483
  4. Phase 1/2 Study to Describe the Safety and Immunogenicity of a COVID-19 RNA Vaccine Candidate (BNT162b1) in Adults 18 to 55 Years of Age: Interim Report, Mulligan et al., (2020) MedRxiv: https://doi.org/10.1101/2020.06.30.20142570
  5. Concurrent human antibody and TH1 type T-cell responses elicited by a COVID-19 RNA vaccine,  Sahin et al., (2020) MedRxiv: https://doi.org/10.1101/2020.07.17.20140533
  6. Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2: a preliminary report of a phase 1/2, single-blind, randomized controlled trial, Folegatti et al., (2020) The Lancet: https://doi.org/10.1016/S0140-6736(20)31604-4
  7. Safety, tolerability, and immunogenicity of a recombinant adenovirus type-5 vectored COVID-19 vaccine: a dose-escalation, open-label, non-randomized, first-in-human trial, Zhu et al., (2020) The Lancet: https://doi.org/10.1016/S0140-6736(20)31208-3
  8. Immunogenicity and safety of a recombinant adenovirus type-5-vectored COVID-19 vaccine in healthy adults aged 18 years or older: a randomised, double-blind, placebo-controlled, phase 2 trial, Zhu et al., (2020) The Lancet: https://doi.org/10.1016/S0140-6736(20)31605-6
  9. Development of an inactivated vaccine candidate for SARS-CoV-2, Q. Gao et al., Science (2020): http://doi.org/10.1126/science.abc1932
  10. ChAdOx1 nCoV-19 vaccination prevents SARS-CoV-2 pneumonia in rhesus macaques, N.v. Doremalen, bioRxiv (2020): https://doi.org/10.1101/2020.05.13.093195
  11. Correlation between universal BCG vaccination policy and reduced morbidity and mortality for COVID-19: an epidemiological study. Miller et al., MedRxiv (2020): https://doi.org/10.1101/2020.03.24.20042937
  12. BCG vaccine protection from severe coronavirus disease 2019 (COVID-19). Escobar et al, (2020):  https://doi.org/10.1073/pnas.2008410117
  13. Considering BCG vaccination to reduce the impact of COVID-19, N. Curtis et al., The Lancet (2020): https://doi.org/10.1016/S0140-6736(20)31025-4
  14. Homologous protein domains in SARS-CoV-2 and measles, mumps and rubella viruses: preliminary evidence that MMR vaccine might provide protection against COVID-19, R. Franklin et al., MedRxiv (2020): https://doi.org/10.1101/2020.04.10.20053207
  15. The BCG World Atlas: A Database of Global BCG Vaccination Policies and Practices, Zwerling et al., (2011): PLoS Medicine: doi: 10.1371/journal.pmed.1001012
  16. Moderna Completes Enrollment of Phase 3 COVE Study of mRNA Vaccine Against COVID-19 (mRNA-1273). Moderna: https://investors.modernatx.com/news-releases/news-release-details/moderna-completes-enrollment-phase-3-cove-study-mrna-vaccine
  17. SARS-CoV-2 vaccines in development. Florian Krammer (2020), Nature: https://www.nature.com/articles/s41586-020-2798-3
  18. Development and Licensure of Vaccines to Prevent COVID-19: Guidance for Industry https://www.fda.gov/media/139638/download
  • City of Hope Initiates Phase 1 Clinical Trial to Test Its First SARS-CoV-2 Investigational Vaccine [Link] (11/25/20)
  • Second interim analysis of clinical trial data showed a 91.4% efficacy for the SPUTNIK V vaccine on day 28 after the first dose; vaccine efficacy is over 95% 42 days after the first dose [Link] (11/25/20)
  • AZD1222 vaccine met primary efficacy endpoint in preventing COVID-19 [Link] (11/25/20)
  • Butantan  vaccine reaches final stage (Sinovac) [Link] (11/25/20)
  • Newcastle disease virus (NDV) expressing the spike protein of SARS-CoV-2 as a live virus vaccine candidate [Link] (11/25/20)
  • Pfizer and  BioNTech to submit emergency use authorization request to the US FDA for COVID-19 vaccine [Link] (11/25/20)
  • Analysis of Measles-Mumps-Rubella (MMR) Titers of Recovered COVID-19 Patients [Link] (11/25/20)
  • AstraZeneca COVID-19 vaccine shows promise in elderly, trial results by Christmas [Link] (11/20/20)
  • Safety and immunogenicity of ChAdOx1 nCoV-19 vaccine administered in a prime-boost regimen in young and old adults (COV002): a single-blind, randomised, controlled, phase 2/3 trial [Link] (11/20/20)
  • Development of CpG-adjuvanted stable prefusion SARS-CoV-2 spike antigen as a subunit vaccine against COVID-19 [Link] (11/20/20)
  • Russia begins post-registration trials of EpiVacCorona Covid-19 vaccine [Link] (11/20/20)
  • Safety, tolerability, and immunogenicity of an inactivated SARS-CoV-2 vaccine in healthy adults aged 18–59 years: a randomised, double-blind, placebo-controlled, phase 1/2 clinical trial [Link] (11/20/20)
  • Immunogenicity of one- and two-dose regimens of the Ad26.COV2.S COVID-19 vaccine candidate in adult and aged rhesus macaques [Link] (11/20/20)
  • European Medicines Agency Begins Rolling Review of Moderna’s mRNA Vaccine Candidate Against COVID-19 (mRNA-1273) [Link] (11/20/20)
  • Biological E. limited starts phase I/II clinical trial of its covid-19 vaccine candidate [Link] (11/20/20)
  • PFIZER AND BIONTECH CONCLUDE PHASE 3 STUDY: Primary efficacy analysis demonstrates BNT162b2 to be 95% effective [Link] (11/19/20)
  • Moderna’s COVID-19 Vaccine Candidate Meets its Primary Efficacy Endpoint in the First Interim Analysis of the Phase 3 COVE Study [Link] (11/18/20)
  • INOVIO Announces Initiation of Phase 2 Segment of its Phase 2/3 Clinical Trial for its COVID-19 DNA Vaccine Candidate, INO-4800; Trial Will Be Funded by the U.S. Department of Defense [Link] (11/18/20)
  • Swissmedic Begins Rolling Review of Moderna’s mRNA Vaccine Against COVID-19 (mRNA-1273) [Link] (11/18/20)
  • Vaxart Announces Additional Data from Hamster Challenge Study of its Oral COVID-19 Vaccine  [Link] (11/18/20)
  • Moderna Has Completed Case Accrual for First Planned Interim Analysis of its mRNA Vaccine Against COVID-19 (mRNA-1273) [Link] (11/13/20)
  • Medicago reports interim results of Phase I trial of Covid-19 vaccine [Link] (11/13/20)
  • The first interim data analysis of the Sputnik V vaccine against COVID-19 phase III clinical trials in the Russian Federation demonstrated 92% efficacy  [Link] (11/13/20)
  • Protective efficacy of a SARS-CoV-2 DNA Vaccine in wild-type and immunosuppressed Syrian hamsters  [Link] (11/13/20)
  • Novavax COVID-19 Vaccine Granted Fast Track Designation by U.S. FDA  [Link] (11/13/20)
  • Phase 1 Assessment of the Safety and Immunogenicity of an mRNA- Lipid Nanoparticle Vaccine Candidate Against SARS-CoV-2 in Human Volunteers  [Link] (11/13/20)
  • Two-component spike nanoparticle vaccine protects macaques from SARS-CoV-2 infection  [Link] (11/13/20)Exosome-Mediated mRNA Delivery For SARS-CoV-2 Vaccination  [Link] (11/13/20)
  • Phase 1 trial of a Candidate Recombinant Virus-Like Particle Vaccine for Covid-19 Disease Produced in Plants  [Link] (11/13/20)
  • Rapid development of SARS-CoV-2 receptor binding domain-conjugated nanoparticle vaccine candidate  [Link] (11/13/20)
  • After an interim phase 3 efficacy analysis, Pfizer and BioNTech announce mRNA-based vaccine candidate, BNT162b2 is 90% effective with no serious safety concerns [Link] (11/09/20)
  • A yeast-expressed SARS-CoV-2 recombinant receptor-binding domain candidate vaccine stimulates virus neutralizing antibodies and T-cell immunity in mice [Link] (11/06/20)
  • Oxford-AstraZeneca’s Phase III COVID-19 vaccine data could be available by December 2020 [Link] (11/06/20)
  • Bahrain becomes the latest country to vaccinate frontline workers with vaccine developed by Sinopharm [Link] (11/06/20)
  • CureVac reports positive interim Phase 1 data for its vaccine candidate CVnCoV with a balanced and strong immune response, 12 ug dose is selected to be tested for Phase 2b/3 [Link] (11/04/20)
  • World′s first triple antigen VLP vaccine candidate induces SARS-CoV-2 specific neutralizing antibodies in mice and with Th1-biased cellular immune responses in PBMCs from convalescent patients [Link] (11/04/20)
  • OZG-38.61.3, a non-adjuvant added, gamma-irradiated, and intradermally applied inactive viral vaccine, confers protection from SARS-CoV-2 in human ACE2-transgenic mice [Link] (11/04/20)


Select promising vaccine candidates currently in clinical trials are detailed below.

Candidate: Non-Replicating Viral Vector AZD1222 (ChAdOx1)

Sponsors/Developers: The University of Oxford, The Jenner Institute | AstraZeneca; BARDA; UK Ministry of Health

Location: UK, Brazil, United States, South Africa, Others.

Trial Identifier: NCT04400838 (COV002, Phase 2/3); ISRCTN: 15281137; NCT04516746 (Phase 2/3); NCT04536051 and ISRCTN89951424 (Phase 3, COV003); NCT04324606 (Phase 1/2); NCT04444674 (Phase 1/2); NCT04540393 (Phase 3); NCT04568031 (Phase 1/2)

Description: ChAdOx1 nCoV-19 (AZD1222) is a replication-defective chimpanzee adenovirus-vectored vaccine expressing the full-length SARS-CoV-2 spike glycoprotein gene (GenBank accession number MN908947). It uses a replication-deficient chimpanzee viral vector based on a weakened version of a common cold virus (adenovirus) that causes infections in chimpanzees and contains the genetic material of the SARS-CoV-2 virus spike protein. After vaccination, the surface spike protein is produced, priming the immune system to attack the SARS-CoV-2 virus if it later infects the body.

Vaccination of rhesus macaques with a single dose of ChAdOx1 nCoV-19 generates humoral and cellular immune responses and protects from lower respiratory infection after subsequent challenge with SARS-CoV-2. AZD1222 was co-invented by the University of Oxford and its spin-out company, Vaccitech.

Preliminary results of a phase 1/2 clinical trial of ChAdOx1 nCoV-19 in adults aged 18-55 years show that the vaccine is well tolerated and generates robust neutralising antibody and cellular immune responses against the spike glycoprotein.

The vaccine platform will also be tested in inhaled form alongside the candidate from Imperial College London.

After an interim safety review, the company on 23 October announced that clinical trials for the AZD1222 have resumed across the world with regulators in the US, UK, Brazil, South Africa and Japan confirming that it was safe to do so.

In the phase 2 component of a single-blind, randomised, controlled, phase 2/3 trial (COV002), healthy adults aged 18 years and older were enrolled at two UK clinical research facilities, in an age-escalation manner, into 18-55 years, 56-69 years, and 70 years and older immunogenicity subgroups. The Phase II trial reported a total of 560 healthy volunteers, with 160 aged 18-55 years, 160 aged 56-69 years, and 240 aged 70 or over. Article published on November 18, 2020 in The Lancet showed ChAdOx1 nCoV-19 appeared to be better tolerated in older adults than in younger adults and has similar immunogenicity across all age groups after a boost dose. Antibody responses against the SARS-CoV-2 spike protein were induced in all age groups and were boosted and maintained at 28 days after booster vaccination, including in the 70 years and older group. Cellular immune responses were also induced in all age and dose groups, peaking at day 14 after vaccination. Local and systemic reactions were more common in participants given ChAdOx1 nCoV-19 than in those given the control vaccine, and similar in nature to those previously reported (injection-site pain, feeling feverish, muscle ache, headache), but were less common in older adults (aged ≥56 years) than younger adults.

“The robust antibody and T-cell responses seen in older people in our study are encouraging,” said Maheshi Ramasamy, a consultant and co-lead investigator at the Oxford Vaccine Group. Late-stage, or Phase III, trials are ongoing to confirm the findings, researchers said, and to test whether the vaccine protects against infection with SARS-CoV-2 in a broad range of people, including people with underlying health conditions.

Status: On 23rd November, the company announced that the AZD1222 vaccine met primary efficacy endpoint in preventing COVID-19.

Positive high-level results from an interim analysis of clinical trials of AZD1222 in the UK and Brazil showed the vaccine was highly effective in preventing COVID-19, the primary endpoint, and no hospitalizations or severe cases of the disease were reported in participants receiving the vaccine. There was a total of 131 COVID-19 cases in the interim analysis. One dosing regimen (n=2,741) showed vaccine efficacy of 90% when AZD1222 was given as a half dose, followed by a full dose at least one month apart, and another dosing regimen (n=8,895) showed 62% efficacy when given as two full doses at least one month apart. The combined analysis from both dosing regimens (n=11,636) resulted in an average efficacy of 70%. All results were statistically significant (p<=0.0001). The Company will seek an Emergency Use Listing from the World Health Organization for an accelerated pathway to vaccine availability in low-income countries. In parallel, the full analysis of the interim results is being submitted for publication in a peer-reviewed journal.

References:

  • Preprint: A single dose of ChAdOx1 MERS provides broad protective immunity against a variety of MERS-CoV strains. bioRxiv (04/13/20).
  • Preprint: SARS-CoV-2 candidate vaccine ChAdOx1 nCoV-19 infection of human cell lines reveals a normal low range of viral backbone gene expression alongside very high levels of SARS-CoV-2 S glycoprotein expression. ResearchSquare (10/20/20).
  • Preprint: A booster dose enhances immunogenicity of the COVID-19 vaccine candidate ChAdOx1 nCoV-19 in aged mice. bioRxiv (10/27/20).
  • Publication: Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2: a preliminary report of a phase 1/2, single-blind, randomised controlled trial. Lancet (07/20/20).
  • Publication: Evaluation of the immunogenicity of prime-boost vaccination with the replication-deficient viral vectored COVID-19 vaccine candidate ChAdOx1 nCoV-19. Nature (07/27/20)
  • Publication: ChAdOx1 nCoV-19 vaccine induced antigen-specific antibody and T cells responses after a single dose and enhanced responses after a booster immunization in mice and pigs. Nature (07/27/20).
  • Publication: ChAdOx1 nCoV-19 vaccine prevents SARS-CoV-2 pneumonia in rhesus macaques. Nature (07/30/20).
  • Publication: A single-dose intranasal ChAd vaccine protects upper and lower respiratory tracts against SARS-CoV-2. Cell (08/19/20).
  • Imperial College: Landmark coronavirus study to trial inhaled Imperial and Oxford vaccines. (09/14/20).
  • Press Release: FDA authorises restart of the COVID-19 AZD1222 vaccine US Phase III trial. Astrazeneca (10/23/20).
  • Protocol: A Phase III Randomized, Double-blind, Placebo-controlled Multicenter Study in Adults to Determine the Safety, Efficacy, and Immunogenicity of AZD1222, a Non-replicating ChAdOx1 Vector Vaccine, for the Prevention of COVID-19. AstraZeneca (09/17/20).
  • News: AstraZeneca COVID-19 vaccine shows promise in elderly, trial results by Christmas. Reuters (11/18/20).
  • Press Release: AZD1222 vaccine met primary efficacy endpoint in preventing COVID-19. Astrazeneca (11/23/20).

Candidate: Four BNT162 Vaccines – BNT162 a1, b1, b2, and c2, BNT162b2 in Phase 3.

Sponsors/Developers: Pfizer | BioNTech RNA Pharmaceuticals GmbH | Fosun Pharma

Location: Germany, U. S.

Trial identifier: NCT04368728 (Phase1/2/3); NCT04380701 (Phase 1/2)

Description: The phase 1 clinical trials began in the U.S. and Germany in April and were designed to evaluate the safety, tolerability, and potential efficacy of up to four mRNA vaccine candidates and to select which vaccine candidate and dose should be taken forward for future clinical study. The BNT162b2 candidate, at a 30-µg dose level in a two vaccination course was selected for phase 2/3 and also received U.S. Food and Drug Administration Fast Track designation.

The two lipid nanoparticle–formulated nucleoside-modified RNA (modRNA) vaccine candidates against SARS-CoV-2 were evaluated in the phase 1 portion of the trial in the United States. One of these candidates, BNT162b1, encodes the SARS-CoV-2 receptor–binding domain, trimerized by the addition of a T4 fibritin foldon domain to increase its immunogenicity through multivalent display.  The other candidate, BNT162b2, encodes the SARS-CoV-2 full-length spike, modified by two proline mutations to lock it in the prefusion conformation and more closely mimic the intact virus with which the elicited virus-neutralizing antibodies must interact.

BNT162b2, which encodes a prefusion stabilized membrane-anchored SARS-CoV-2 full-length spike was selected over BNT162b1, which encodes a secreted trimerized RBD for Phase 2/3. Additional safety and immunogenicity data were presented from the US Phase 1 trial that supported selection of the vaccine candidate advanced to a pivotal Phase 2/3 safety and efficacy evaluation. BNT162b2 was associated with less systemic reactogenicity, particularly in older adults. In both younger and older adults, the 2 vaccine candidates elicited similar dose-dependent neutralizing titers , higher than convalescent sera.

Immunization of mice with a single dose of BNT162b2 induced dose level-dependent increases in pseudovirus neutralization titers. Prime-boost vaccination of rhesus macaques elicited authentic SARS-CoV-2 neutralizing geometric mean titers 10.2 to 18.0 times that of a SARS-CoV-2 convalescent human serum panel. BNT162b2 generated strong TH1 type CD4+ and IFNg+ CD8+ T-cell responses in mice and rhesus macaques. The BNT162b2 vaccine candidate fully protected the lungs of immunized rhesus macaques from infectious SARS-CoV-2 challenge.

The Phase 3 portion of the clinical trial was designed to determine if the BNT162b2 vaccine candidate is safe and effective in preventing COVID-19 disease. This part of the trial began July 27 and is estimated to enroll up to 44,000 participants. If successful, the next step will be to seek regulatory review and emergency use authorization or approval. In September 2020, Pfizer expanded the enrollment of its Phase 3 pivotal COVID-19 vaccine trial to approximately 44,000 participants. This allowed for the enrollment of new populations, including adolescents as young as 16 years of age and people with chronic, stable HIV (human immunodeficiency viruses), Hepatitis C, or Hepatitis B infection. In October 2020, Pfizer received permission from the FDA to enroll adolescents as young as 12. The Phase 3 clinical trial of BNT162b2 has enrolled 43,538 participants to date, 38,955 of whom have received a second dose of the vaccine candidate as of November 8, 2020.

On 6 October, BioNTech and Pfizer initiated a rolling submission to European Medicines Agency for the candidate BNT162b2 and plan to work with the EMA’s Committee for Medicinal Products for Human Use (CHMP) to complete the rolling review process to facilitate the final Marketing Authorization Application (MAA).

On November 09, 2020, following an interim phase 3 efficacy analysis, Pfizer and BioNTech announced that the mRNA-based vaccine candidate, BNT162b2 was found to be more than 90% effective in preventing COVID-19 in participants without evidence of prior SARS-CoV-2 infection in the first interim efficacy analysis. Analysis evaluated 94 confirmed cases of COVID-19 in trial participants.

Status: A final analysis of the Phase 3 trial  shows it was 95% effective in preventing infections, even in older adults, and caused no serious safety concerns, the company said on November 18, 2020. The company counted 170 cases of coronavirus infection among volunteers who took part in the trial. It said 162 infections were in people who got placebo, or plain saline shots, while eight cases were in participants who got the actual vaccine. That works out to an efficacy of 95%, Pfizer said. Data demonstrate vaccine was well tolerated across all populations with over 43,000 participants enrolled; no serious safety concerns observed; the only Grade 3 adverse event greater than 2% in frequency was fatigue at 3.8% and headache at 2.0%. The companies expect to produce globally up to 50 million vaccine doses in 2020 and up to 1.3 billion doses by the end of 2021. Pfizer is confident in its vast experience, expertise and existing cold-chain infrastructure to distribute the vaccine around the world.

References:

  • Preprint: Phase 1/2 Study to Describe the Safety and Immunogenicity of a COVID-19 RNA Vaccine Candidate (BNT162b1) in Adults 18 to 55 Years of Age: Interim Report. medRxiv (07/01/20).
  • Press Release: Pfizer and BioNTech Granted FDA Fast Track Designation for Two Investigational mRNA-based Vaccine Candidates Against SARS-CoV-2. Businesswire (07/13/20).
  • Preprint: Concurrent human antibody and TH1 type T-cell responses elicited by a COVID-19 RNA vaccine. medRxiv (07/20/20).
  • Press Release: PFIZER and BIONTECH announce agreement with the United Kingdom for 30 million doses of mRNA-based vaccine candidate against SARS-COV-2. Pfizer (07/20/20).
  • Press Release: Pfizer and BioNTech Choose Lead mRNA Vaccine Candidate Against COVID-19 and Commence Pivotal Phase 2/3 Global Study. BioNTech (07/27/20).
  • Publication: Phase 1/2 study of COVID-19 RNA vaccine BNT162b1 in adults. Nature (08/12/20).
  • Publication: RNA-Based COVID-19 Vaccine BNT162b2 Selected for a Pivotal Efficacy Study. medRxiv (08/21/20).
  • Preprint: A prefusion SARS-CoV-2 spike RNA vaccine is highly immunogenic and prevents lung infection in non-human primates. bioRxiv (09/19/20).
  • Press Release: PFIZER AND BIONTECH PROPOSE EXPANSION OF PIVOTAL COVID-19 VACCINE TRIAL. Pfizer (09/12/20).
  • Reuters: Pfizer says Covid-19 vaccine showed moderate side effects. Reuters (09/16/20).
  • Publication: COVID-19 vaccine BNT162b1 elicits human antibody and TH1 T-cell responses. Nature (09/30/20).
  • Press Release: BioNTech and Pfizer Initiate Rolling Submission to European Medicines Agency for SARS-CoV-2 Vaccine Candidate BNT162b2. BioNtech (10/06/20).
  • Press Release: PFIZER AND BIONTECH ANNOUNCE VACCINE CANDIDATE AGAINST COVID-19 ACHIEVED SUCCESS IN FIRST INTERIM ANALYSIS FROM PHASE 3 STUDY. Pfizer (11/09/20).
  • Press Release: PFIZER AND BIONTECH CONCLUDE PHASE 3 STUDY OF COVID-19 VACCINE CANDIDATE, MEETING ALL PRIMARY EFFICACY ENDPOINTS. Pfizer (11/18/20).

Candidate: Lipid nanoparticle (LNP) encapsulated mRNA (mRNA-1273)

Sponsors/Developers: Moderna, Inc. | National Institute of Allergy and Infectious Diseases (NIAID); Funding from the Biomedical Advanced Research and Development Authority (BARDA); Kaiser Permanente Washington Health Research Institute

Location: U.S.

Trial identifier: NCT04283461 (Phase 1) NCT04405076 (Phase 2), NCT04470427 (COVE, Phase 3)

Description: mRNA-1273 is an mRNA vaccine encoding for a prefusion stabilized form of the Spike (S) protein, which was selected by Moderna in collaboration with investigators from Vaccine Research Center (VRC) at the NIAID. This vaccine encodes a stabilized version of the SARS-CoV-2 full-length spike glycoprotein trimer, S-2P, which has been modified to include two proline substitutions at the top of the central helix in the S2 subunit. The mRNA is encapsulated in lipid nanoparticles at a concentration of 0.5 mg per milliliter and diluted with normal saline to achieve the final target vaccine concentrations. The first clinical batch, which was funded by the Coalition for Epidemic Preparedness Innovations, was completed on February 7, 2020 and underwent analytical testing; it was shipped to NIH on February 24, 42 days from sequence selection. The first participant in the NIAID-led Phase 1 study of mRNA-1273 was dosed on March 16, 63 days from sequence selection to Phase 1 study dosing.

On May 12, the FDA granted mRNA-1273 Fast Track designation. On May 29, the first participants in each age cohort: adults ages 18-55 years (n=300) and older adults ages 55 years and above (n=300) were dosed in the Phase 2 study of mRNA-1273. On July 8, the Phase 2 study completed enrollment.

Results from the second interim analysis of mRNA-1273 in the 56-70 and 71+ age groups were published on September 29 in The New England Journal of Medicine. On July 28, results from a non-human primate preclinical viral challenge study evaluating mRNA-1273 were published in The New England Journal of Medicine. On July 14, an interim analysis of the original cohorts in the NIH-led Phase 1 study of mRNA-1273 was published in The New England Journal of Medicine.

Interim results were published in The New England Journal of Medicine of interim results from older adult age cohorts in Phase 1 Study. mRNA-1273 induced consistently high levels of pseudovirus neutralization antibody titers in all participants in the 56-70 (n=10) and 71+ (n=10) age cohorts. Potent neutralization responses were confirmed by 3 different live virus assays. mRNA-1273 elicited Th1-biased CD4 T cell responses in the 56-70 and 71+ age cohorts. Neutralizing antibody titers and T cell responses in the 56-70 and 71+ age cohorts were consistent with those reported in younger adults. At the 25 ug and 100 ug dose levels, mRNA-1273 was generally well-tolerated in all age cohorts.

The Phase 3 COVE study was designed in collaboration with the FDA and NIH to evaluate Americans at the highest risk of severe COVID-19 disease. As of today, the COVE study includes more than 7,000 Americans over the age of 65. It also includes more than 5,000 Americans who are under the age of 65 but have high-risk chronic diseases that put them at increased risk of severe COVID-19, such as diabetes, severe obesity and cardiac disease. These medically high-risk groups represent 42% of the total participants in the Phase 3 COVE study.

Moderna on October 22 announced that it has completed enrollment of 30,000 participants for the Phase 3 COVE study of mRNA-1273. And that more than 25,650 participants have received their second vaccination. Moderna will determine whether to submit a dossier to FDA requesting Emergency Use Authorization based on an assessment of whether the potential benefit of the vaccine outweighs the potential risks once the 2 months of median safety follow-up have accrued. As on November 11, Moderna has seen a significant increase in the rate of case identification across sites in the last week. As a result, the Company expects the first interim analysis will include substantially more than 53 cases, the targeted trigger point for the analysis. The data on these cases is being prepared for submission to the independent Data Safety Monitoring Board (DSMB) for analysis and recommendation. Moderna remains blinded to whether these participants received vaccine or placebo.

Status: Moderna on 16 November 2020 announced that the independent DSMB for the Phase 3 study has informed that the trial has met the statistical criteria pre-specified in the study protocol for efficacy, with a vaccine efficacy of 94.5%. The primary endpoint of the Phase 3 COVE study is based on the analysis of COVID-19 cases confirmed and adjudicated starting two weeks following the second dose of vaccine. This first interim analysis was based on 95 cases, of which 90 cases of COVID-19 were observed in the placebo group versus 5 cases observed in the mRNA-1273 group, resulting in a point estimate of vaccine efficacy of 94.5% (p <0.0001). The 95 COVID-19 cases included 15 older adults (ages 65+) and 20 participants identifying as being from diverse communities (including 12 Hispanic or LatinX, 4 Black or African Americans, 3 Asian Americans and 1 multiracial). Moderna also announced that the vaccine candidate is now expected to remain stable at standard refrigerator temperatures of 2° to 8°C (36° to 46°F) for 30 days, up from previous estimate of 7 days. Statement also mentioned shipping and long-term storage conditions at standard freezer temperatures of -20°C (-4°F) for 6 months. The European Medicines Agency (EMA) human medicines committee (CHMP) has started a rolling review of mRNA-1273.

References:

  • Publication: An mRNA Vaccine against SARS-CoV-2 – Preliminary Report. NEJM (07/14/20).
  • Preprint: mRNA-1273 induces both potent neutralizing antibody and CD8 T cell responses and protects against SARS-CoV-2 infection in lungs and noses of mice without evidence of immunopathology. bioRxiv (06/11/20).
  • Press Release: Moderna Announces Expansion of BARDA Agreement to Support Larger Phase 3 Program for Vaccine (mRNA-1273) Against COVID-19. Moderna (07/26/20).
  • Publication: Evaluation of the mRNA-1273 Vaccine against SARS-CoV-2 in Nonhuman Primates. NEJM (07/28/20).
  • Press Release: Moderna says its coronavirus vaccine shows promising results in small trial of elderly patients. Moderna (08/27/20).
  • Website: Additional COVE Study Information. Moderna (Accessed 09/25/20).
  • Publication: Safety and Immunogenicity of SARS-CoV-2 mRNA-1273 Vaccine in Older Adults. NEJM (09/29/20).
  • Press Release: Moderna Completes Enrollment of Phase 3 COVE Study of mRNA Vaccine Against COVID-19 (mRNA-1273). Moderna (10/22/20).
  • Press Release: Moderna Has Completed Case Accrual for First Planned Interim Analysis of its mRNA Vaccine Against COVID-19 (mRNA-1273). Moderna (11/11/20).
  • Press Release: Moderna’s COVID-19 Vaccine Candidate Meets its Primary Efficacy Endpoint in the First Interim Analysis of the Phase 3 COVE Study. Moderna (11/16/20).
  • Press Release:  Moderna Announces Longer Shelf Life for its COVID-19 Vaccine Candidate at Refrigerated Temperatures. Moderna (11/16/20).
  • Press Release: European Medicines Agency Begins Rolling Review of Moderna’s mRNA Vaccine Candidate Against COVID-19 (mRNA-1273). Moderna (11/17/20).

Candidate: Protein subunit; NVX-CoV2373; Full-length recombinant SARS COV-2 glycoprotein nanoparticle vaccine adjuvanted with Matrix M

Sponsors/Developers: Novavax, Inc.

Location: Australia; South Africa; U. K.

Trial identifier: NCT04368988 (Phase 2); NCT04533399 (Phase 2)

Description: NVX-CoV2373 is a stable, prefusion protein made using Novavax’ proprietary nanoparticle technology.

NVX-CoV2373 was created using Novavax’ recombinant nanoparticle technology to generate antigen derived from the coronavirus spike (S) protein and contains Novavax’ patented saponin-based Matrix-M™ adjuvant to enhance the immune response and stimulate high levels of neutralizing antibodies. NVX-CoV2373 contains purified protein antigen and cannot replicate, nor can it cause COVID-19. In preclinical trials, NVX-CoV2373 demonstrated induction of antibodies that block binding of spike protein to receptors targeted by the virus, a critical aspect for effective vaccine protection. In the Phase 1 portion of its Phase 1/2 clinical trial, NVX-CoV2373 was generally well-tolerated and elicited robust antibody responses numerically superior to that seen in human convalescent sera. NVX-CoV2373 is also being evaluated in a Phase 3 trial in the UK and two ongoing Phase 2 studies that began in August; a Phase 2b trial in South Africa, and a Phase 1/2 continuation in the U.S. and Australia. Novavax has secured $2 billion in funding for its global coronavirus vaccine program, including up to $399 million in funding from the Coalition for Epidemic Preparedness Innovations (CEPI) and almost $1.7 billion from the U.S. government.

Novavax has enrolled over 5,500 participants to date in the United Kingdom (U.K.) trial, which it has expanded to 15,000 volunteers. The increased enrollment is likely to facilitate assessment of safety and efficacy in a shorter time period.

Status: Novavax on November 09, 2020 announced that the U.S. Food and Drug Administration (FDA) has granted Fast Track Designation for NVX-CoV2373. Novavax expects to begin its pivotal Phase 3 clinical trial in the United States and Mexico by the end of November. Data from the event-driven trial could support global authorization and approval, including in the U.S. The Company’s ongoing Phase 3 clinical trial in the UK is expected to be fully enrolled by the end of November. Depending on the overall COVID-19 attack rate, interim data in the UK trial, which is also event-driven, are expected as soon as early first quarter 2021.

References:

  • Press Release: Novavax Announces $1.6 Billion Funding from Operation Warp Speed. Novavax (07/07/20).
  • Press Release: Novavax and FUJIFILM Diosynth Biotechnologies Initiate Large Scale Manufacturing of COVID-19 Vaccine Candidate. Novavax (07/23/20).
  • Press Release: Novavax Announces Positive Phase 1 Data for its COVID-19 Vaccine Candidate. Novavax (08/05/20).
  • Press Release: Novavax and Takeda Announce Collaboration for Novavax’ COVID19 Vaccine in Japan. Novavax (08/06/20).
  • Press Release: Novavax Initiates Efficacy Trial of COVID-19 Vaccine in South Africa. Novavax (08/17/20).
  • Press Release: Novavax Initiates Phase 2 Portion of Phase 1/2 Clinical Trial of COVID-19 Vaccine. Novavax (08/24/20).
  • Publication: Phase 1-2 Trial of a SARS-CoV-2 Recombinant Spike Protein Nanoparticle Vaccine. NEJM (09/02/20).
  • Press Release: Novavax Announces COVID-19 Vaccine Manufacturing Agreement with Serum Institute of India, Increasing Novavax’ Global Production Capacity to Over 2 Billion Doses Annually. Novavax (09/15/20).
  • Press Release: Novavax Initiates Phase 3 Efficacy Trial of COVID-19 Vaccine in the United Kingdom. Novavax (09/24/20).
  • Publication: SARS-CoV-2 spike glycoprotein vaccine candidate NVX-CoV2373 elicits immunogenicity in baboons and protection in mice. bioRxiv Preprint (06/30/20).
  • Publication: Structural analysis of full-length SARS-CoV-2 spike protein from an advanced vaccine candidate. Science (10/20/20).
  • Publication: NVX-CoV2373 vaccine protects cynomolgus macaque upper and lower airways against SARS-CoV-2 challenge. Vaccine (10/23/20).
  • Press Release: Novavax Provides Phase 3 COVID-19 Vaccine Clinical Development Update. Novavax (10/27/20).
  • Press Release: Novavax COVID-19 Vaccine Granted Fast Track Designation by U.S. FDA. Novavax (11/09/20).

Candidate: Inactivated virus (CoronaVac/PiccoVac)

Sponsors/Developers: Sinovac Biotech Ltd.; Funding by Advantech Capital and Vivo Capital

Location: Brazil, Turkey, Indonesia, China

Trial identifier: NCT04456595 (Phase 3), NCT04352608 (Phase 2), NCT04508075 (Phase 3), NCT04551547 (Phase 1/2), NCT04383574 (Phase 1/2), NCT04582344 (Phase 3)

Description: CoronaVac (Sinovac Life Sciences, Beijing, China) is an inactivated vaccine candidate against COVID-19 that has shown good immunogenicity in mice, rats, and non-human primates with vaccine-induced neutralising antibodies to SARS-CoV-2, which could neutralize ten representative strains of SARS-CoV-2. Moreover, the results indicated CoronaVac provided partial or complete protection in macaques from severe interstitial pneumonia after a SARS-CoV-2 challenge, without observable antibody-dependent enhancement of infection, which support progression to clinical trials in humans.

The candidate was granted an emergency use authorisation by Chinese authorities in July 2020, before the initiation of phase 3 studies. This authorisation reportedly resulted in nearly 90% of company employees being immunised with the vaccine.

Phase 1/2 clinical trials, which enrolled healthy volunteers aged 18–59 years, have been completed (eg, NCT04352608). The phase 1 trial included 143 participants. In the phase 2 trial, 600 participants were randomly assigned to receive, in two intramuscular injections, either 3 μg per 0·5 mL or 6 μg per 0·5 mL of the trial vaccine, or placebo, either on day 0 and day 14, or on day 0 and day 28. No serious adverse events were reported. The vaccine elicited anti-RBD antibodies, as measured by ELISA, and neutralising antibodies 14 days after the second dose of vaccine in 92·4% of individuals receiving the vaccine at 0 and 14 days, and in 97·4% of those receiving the vaccine at 0 and 28 days. Importantly, neutralising antibody responses were significantly higher in younger adults (aged 18–39 years) than in older adults (aged 40–59 years), and stronger responses were noted in participants given the second dose on day 28 than in those given the second dose on day 14. A phase 3 trial was launched in Brazil and Indonesia, with the trial in Brazil aiming to enrol 9000 health-care personnel.

Sinovac announced on 23 September that CoronaVac was approved by the National Medical Products Administration (NMPA) for clinical trial in adolescents and children. This randomized, double-blinded, and placebo-controlled phase I/II clinical trial among adolescents and children between the ages of 3-17 years old was approved by the Ethics Committee of the Hebei Provincial CDC on September 11, 2020, with the trial expected to commence soon. In this clinical trial, low dosage (300SU/dose) and medium dosage (600SU/dose) with two-dose immunization scheduled at 28-day intervals will be adapted.

As per news reports, research with 50,027 volunteers in China showed that the Coronavac vaccine did not show significant adverse reactions. Among people over 60 (422 volunteers), the results showed 97% effectiveness. Instituto Butantan is conducting clinical trials of the vaccine in phase 3 in Brazil on almost 6,000 volunteers. In Brazil, the vaccine was applied to almost 5,600 volunteers with no record of serious adverse reaction.

Status: CoronaVac triggered a quick immune response but the level of antibodies produced was lower than in convalescent individuals, as per preliminary trial results published on November 17, 202o. While the early to mid-stage trials were not designed to assess the efficacy of CoronaVac, the team suggest it could provide enough protection, based on their experience with other vaccines and data from preclinical studies with macaques. The Sinovac findings, published in a peer-reviewed paper in medical journal The Lancet Infectious Diseases, came from results in Phase I and Phase II clinical trials in China involving more than 700 participants.

References:

  • News: In Coronavirus Vaccine Race, China Strays From the Official Paths. The NewYork Times (07/16/20)
  • Press Release: Sinovac COVID-19 Vaccine Collaboration with Butantan Receives Approval from Brazilian Regulator for Phase III Trial. Businesswire (06 July 2020).
  • Press Release: Sinovac Announces Positive Preliminary Results of Phase I/II Clinical Trials for Inactivated Vaccine Candidate Against COVID-19. Sinovac (06/13/20).
  • Press Release:  Sinovac and Butantan Join Efforts to Advance the Clinical Development of An Inactivated Vaccine for COVID-19 to Phase III (06/11/20).
  • Publication: Development of an inactivated vaccine candidate for SARS-CoV-2. Science (07/03/20).
  • Preprint: Immunogenicity and Safety of a SARS-CoV-2 Inactivated Vaccine in Healthy Adults Aged 18-59 years: Report of the Randomized, Double-blind, and Placebo-controlled Phase 2 Clinical Trial. medRxiv (08/11/20).
  • News: Sinovac’s vaccine reportedly shows low adverse events following emergency use authorization. News (08/31/20).
  • Press Release: Sinovac’s Coronavac, SARS-CoV-2 Vaccine (Vero Cell), Inactivated, Announces Approval for Phase I/II Clinical Trial in Adolescents and Children. Businesswire (09/23/20).
  • News: Study of more than 50,000 volunteers in China shows Coronavac safety. Sao Paulo’s State Government (09/23/20).
  • Press Release: Sinovac’s Coronavac, SARS-CoV-2 Vaccine (Vero Cell), Inactivated, Announces Approval for Phase I/II Clinical Trial in Adolescents and Children. Businesswire (09/23/20).
  • Publication: Double-Blind, Randomized, Placebo-Controlled Phase III Clinical Trial to Evaluate the Efficacy and Safety of treating Healthcare Professionals with the Adsorbed COVID-19 (Inactivated) Vaccine Manufactured by Sinovac – PROFISCOV: A structured summary of a study protocol for a randomised controlled trial. BMC Trials (10/15/20)
  • Publication: Safety, tolerability, and immunogenicity of an inactivated SARS-CoV-2 vaccine in healthy adults aged 18–59 years: a randomised, double-blind, placebo-controlled, phase 1/2 clinical trial. The Lancet Infectious Diseases (11/17/20).

Candidate: Adenovirus type 26 based vaccine Ad26.COV2.S.

Sponsors/Developers: Janssen Vaccines & Prevention B.V (Johnson & Johnson), Beth Israel Deaconess Medical Center.

Location: United States, United Kingdom, Belgium, Brazil, Japan, Others

Trial identifier: NCT04509947 (Phase 1); NCT04436276 (Phase1/2); NCT04614948 (Phase 3, ENSEMBLE 2); EudraCT Number: 2020-001483-28 (Phase 1/2a); EudraCT Number: 2020-002584-63 (Phase 2a)

Description: Ad26 vector encoding for a membrane-bound stabilized S protein with a wild type signal peptide.

The company’s large-scale, pivotal, multi-country Phase 3 trial (ENSEMBLE) for its COVID-19 vaccine candidate, JNJ-78436735 was initiated following positive interim results from the Company’s Phase 1/2a clinical study, which demonstrated that the safety profile and immunogenicity after a single vaccination were supportive of further development. Based on these results and following discussions with the U.S. Food and Drug Administration (FDA), ENSEMBLE will enroll up to 60,000 volunteers across three continents and will study the safety and efficacy of a single vaccine dose versus placebo in preventing COVID-19.

The Janssen COVID-19 vaccine candidate leverages the Company’s AdVac technology platform, which was also used to develop and manufacture Janssen’s European Commission approved Ebola vaccine and construct its Zika, RSV, and HIV vaccine candidates. Janssen’s AdVac technology platform has been used to vaccinate more than 100,000 people to date across Janssen’s investigational vaccine programs. With Janssen’s AdVac technology, the vaccine, if successful, is estimated at launch to remain stable for two years at -20 °C and at least three months at 2-8° C.

Status:

The Phase 3 ENSEMBLE study of the single-dose regimen continues to enroll and vaccinate study participants. ENSEMBLE is proceeding to enroll up to 60,000 participants worldwide.

In addition to the single-dose regimen ENSEMBLE study, Janssen has now initiated the two-dose regimen ENSEMBLE 2 trial. ENSEMBLE 2 is a complementary, planned, pivotal, large-scale, multi-country Phase 3 trial that will study the safety and efficacy of a two-dose regimen of the investigational Janssen vaccine candidate for the prevention of COVID-19 in up to 30,000 participants worldwide. The ENSEMBLE and ENSEMBLE 2 trials will run in parallel.

References:

  • Press release: Johnson & Johnson Announces Acceleration of its COVID-19 Vaccine Candidate; Phase 1/2a Clinical Trial to Begin in Second Half of July. Johnson & Johnson (06/10/20).
  • Publication: Ad26-vector based COVID-19 vaccine encoding a prefusion stabilized SARS-CoV-2 Spike immunogen induces potent humoral and cellular immune responses. Nature (09/28/20).
  • Publication: Ad26 vaccine protects against SARS-CoV-2 severe clinical disease in hamsters. Nature (09/03/20).
  • Publication: Single-shot Ad26 vaccine protects against SARS-CoV-2 in rhesus macaques. Nature (07/30/20).
  • Press Release: Johnson & Johnson Initiates Pivotal Global Phase 3 Clinical Trial of Janssen’s COVID-19 Vaccine Candidate. JnJ (09/23/20).
  • Preprint: Safety and immunogenicity of the Ad26.COV2.S COVID-19 vaccine candidate: interim results of a phase 1/2a, double-blind, randomized, placebo-controlled trial. medRxiv (09/25/20).
  • Preprint: Immunogenicity of one- and two-dose regimens of the Ad26.COV2.S COVID-19 vaccine candidate in adult and aged rhesus macaques. bioRxiv (11/17/20).
  • Press Release: Johnson & Johnson Initiates Second Global Phase 3 Clinical Trial of its Janssen COVID-19 Vaccine Candidate. Johnson & Johnson (11/15/20).
  • Protocol: A Randomized, Double-blind, Placebo-controlled Phase 3 Study to Assess the Efficacy and Safety of Ad26.COV2.S for the Prevention of SARS-CoV-2-mediated COVID-19 in Adults Aged 18 Years and Older. Janssen Vaccines (09/15/20).

Candidate: Whole-Virion Inactivated SARS-CoV-2 Vaccine (BBV152, Covaxin)

Sponsors/Developers: Bharat Biotech International Limited, ICMR (Indian Council of Medical Research).

Location: India.

Trial identifier: NCT04471519 (Phase1/2), CTRI/2020/07/026300 (Phase 1/2), CTRI/2020/11/028976 (Phase 3)

Description: COVAXIN, Indias COVID-19 vaccine by Bharat Biotech is developed in collaboration with the ICMR – National Institute of Virology (NIV). The indigenous, inactivated vaccine is developed and manufactured in Bharat Biotechs BSL-3 (Bio-Safety Level 3) high containment facility. The vaccine received DCGI approval for Phase I and II Human Clinical Trials and the trials will commence across India from July 2020.

As on August 17, Covaxin has demonstrated an encouraging safety profile in a Phase I clinical trial conducted in the country. Preliminary Phase I trial results showed that the vaccine is safe. Trial investigators are said to be collecting blood samples to analysze the vaccine’s immunogenicity. The Phase I study involves 375 volunteers at 12 sites across the country.

COVAXIN has been evaluated in ~ 1000 subjects in Phase I and Phase II clinical trials, with promising safety and immunogencity data.

The published preprint on the development and evaluation of safety and immunogenicity of this whole virion inactivated SARS-CoV-2 vaccine, adjuvanted with aluminium hydroxide gel (Algel), or a novel TLR7/8 agonist adsorbed Algel. BBV152 vaccine formulations generated significantly high antigen-binding and neutralizing antibody titers, at both concentrations (3 ug and 6 ug), in all three species (mice, rats, and rabbits) with excellent safety profiles. The inactivated vaccine formulation containing TLR7/8 agonist adjuvant-induced Th1 biased antibody responses with elevated IgG2a/IgG1 ratio and increased levels of SARS-CoV-2 specific IFN-g+ CD4 T lymphocyte response.

Bharat Biotech in September said it entered into a licensing agreement with Washington University School of Medicine in St. Louis for a novel ‘chimp-adenovirus’ (Chimpanzee adenovirus), single dose intranasal vaccine for Covid-19. Bharat Biotech also announced it will use adjuvant Alhydroxiquim-II to boost immune response and longer lasting immunity. The technology is being used under licensing agreement with Kansas-based ViroVax LLC.

Status: Bharat Biotech has announced commencement of Phase III trials of COVAXIN on November 16, 2020. The Phase III trials will involve 26,000 volunteers across India, conducted in partnership with ICMR. It is the largest clinical trial conducted for a COVID-19 vaccine in India. Trial volunteers will receive two intramuscular injections approximately 28 days apart. Participants will be randomly assigned to receive COVAXIN™ or placebo. The trial is double blinded.

References:

  • Preprint: Evaluation of Safety and Immunogenicity of an Adjuvanted, TH-1 Skewed, Whole Virion Inactivated SARS-CoV-2 Vaccine – BBV152. bioRxiv (09/09/20).
  • Preprint: Immunogenicity and protective efficacy of BBV152: a whole virion inactivated SARS CoV-2 vaccine in the Syrian hamster model. Research Square (09/16/20).
  • Press Release: Bharat Biotech, Thomas Jefferson University pursue a promising vaccine candidate against COVID-19. Bharat Biotech (05/20/20).
  • Press Release: COVAXIN to boost the immune response and longer-lasting immunity with ViroVax’s adjuvant. Bharat Biotech (10/05/20).
  • News: Washington University School of Medicine in St. Louis Licenses Inhalable COVID-19 Vaccine to India’s Bharat Biotech. TrialSiteNews (09/28/20).
  • Press Release: Bharat Biotech starts Phase III trials for COVAXIN. Bharat Biotech (11/16/20).

Candidate: Inactivated SARS-CoV-2 vaccine BBIBP-CorV

Sponsors/Developers: Sinopharm, Wuhan Institute of Biological Products, China National Biotec Group Company Limited, G42 Healthcare company, Abu Dhabi Health Services Company

Location: UAE, Bahrain, Peru, Morocco, Argentina

Trial identifier: ChiCTR2000034780 (Phase 3); ChiCTR2000032459 (phase 1/2); NCT04510207 (Phase 3); NCT04560881 (Phase 3); ChiCTR2000039000 (Phase 3); NCT04612972 (Phase 3)

Description: Three SARS-CoV-2 strains from the BAL samples or throat swabs of 3 hospitalized patients from the recent COVID-19 outbreak were isolated to develop preclinical in vitro neutralization and challenge models for an inactivated SARS-CoV-2 vaccine candidate (from Vero cells). The 19nCoV-CDC-Tan-HB02 (HB02) strain showed the most optimal replication and generated highest virus yields in Vero cells among three viral strains and was used for the further development of the inactivated SARS-CoV-2 vaccine (BBIBP-CorV). BBIBP-CorV induced high levels of neutralizing antibodies titers in animal models. Two-dose immunization with 2 ug/dose BBIBP-CorV efficiently protects rhesus macaques. It is efficiently produced, genetically stable, and seems to be safe in animals

The first WHO enlisted global clinical Phase III trial of Sinopharm CNBG’s inactivated vaccine to combat COVID-19 started in July in Abu Dhabi. UAE Health Authorities issued a permit for up to 15,000 volunteers to participate and G42 Healthcare and SEHA are working towards achieving a minimum of 5,000 participants for the trials. Sinopharm launched the Phase 3 trials in the UAE in July, and in Peru and Morocco the following month. Sinopharm’s chairman said in August that the vaccine could potentially be ready for public use by the end of 2020.

As on August 12, 2020, the Phase III trials of the inactivated vaccine in the UAE have reached the target of 15,000 volunteers in less than a month, with individuals from 102 nationalities participating in the program. Sinopharm Group Biological Products, noted, “The speed of these trials to date and the incredible diversity of volunteers who have been vaccinated has fully reinforced our decision that the UAE was a perfect location to test our inactivated vaccine and reach the widest demographic range of volunteers.”.

The report on the preliminary assessment of the safety outcomes 28 days and immunogenicity outcomes 14 days after 3 doses in a phase 1 trial and 2 doses in a phase 2 trial of an inactivated COVID-19 vaccine candidate in healthy adults in China was published on August 13, 2020. Patients had a low rate of adverse reactions (only 15% of people in total; fever = 3%) and demonstrated immunogenicity; the study is ongoing. Efficacy and longer-term adverse event assessment will require phase 3 trials. A phase 3 trial has been initiated (ChiCTR2000034780), which will provide information on immune persistence and efficacy.

The UAE’s phase 3 trial was fully recruited by August 30 with 31,000 people having participated altogether since July 16, with 120 nationalities. The UAE had granted an Emergency Use Authorization six weeks after late-stage studies began. The health authorities said the experimental vaccine would be administered to frontline healthcare workers who are dealing with cases of COVID-19 and are at higher risk of exposure.

Status:

Nearly one million people have taken an experimental coronavirus vaccine developed by China National Pharmaceutical Group (Sinopharm) through the country’s emergency use programme, the firm said. No serious adverse reaction has been reported from those who received the vaccine in emergency use, Sinopharm said in an article on social media WeChat, citing Chairman Liu Jingzhen from a recent media interview. The experimental vaccines are undergoing Phase 3 clinical trials overseas that have recruited nearly 60,000 people, and blood samples of more than 40,000 participants have been taken 14 days after they took the second dose, the article said.

References:

  • Publication: Development of an Inactivated Vaccine Candidate, BBIBP-CorV, with Potent Protection against SARS-CoV-2. Cell (08/06/20).
  • Publication: Effect of an Inactivated Vaccine Against SARS-CoV-2 on Safety and Immunogenicity Outcomes: Interim Analysis of 2 Randomized Clinical Trials. JAMA (08/13/20).
  • Publication: Safety and immunogenicity of an inactivated SARS-CoV-2 vaccine, BBIBP-CorV: a randomised, double-blind, placebo-controlled, phase 1/2 trial. The Lancet Infectious Diseases (10/15/20).
  • News: World’s First Phase III Clinical Trial of COVID-19 Inactivated Vaccine Begins in UAE. Businesswire (07/17/20).
  • News: UAE’s phase III Covid-19 inactivated vaccine trial (Sinopharm) reaches milestone of 15,000 volunteers. Khaleejtimes (08/12/20).
  • News: China Sinopharm’s COVID-19 vaccine starts phase-3 clinical trials in Argentina. CGTN (08/22/20).
  • News: Bahrain starts Phase III trial of Sinopharm’s Covid-19 vaccine. Clinicaltrialsarena (08/24/20).
  • News: 31,000 volunteers take part in UAE vaccine trials. The National (08/24/20).
  • News: UAE announces emergency approval for use of COVID-19 vaccine. BioSpace (09/14/20).
  • News: China Sinopharm’s coronavirus vaccine taken by about a million people in emergency use. Reuters (11/19/20).

Candidate: Sputnik V (Gam-COVID-Vac)

Sponsors/Developers: Gamaleya National Research Institute of Epidemiology and Microbiology

Location: Russia, a number of Middle Eastern (UAE and Saudi Arabia), and Latin American countries (Brazil and Mexico).

Trial identifier: NCT04437875 (Phase 1/2), NCT04436471 (Phase 1/2), NCT04530396 (Phase 3)

Description: Russian adenovirus vector-based vaccine was registered by the Russian Ministry of Health on August 11 and became the first registered COVID-19 vaccine on the market. The Gamaleya Center successfully developed and registered an adenoviral vector-based vaccine against Ebola. Another adenoviral vector-based vaccine against Middle East Respiratory Syndrome (MERS) is in advanced stages of clinical trials.

As per the developers, Phase 1 and 2 clinical trials of the vaccine have been completed on August 1, 2020. All the volunteers are feeling well, no unforeseen or unwanted side effects were observed. The vaccine induced strong antibody and cellular immune response. Not a single participant of the current clinical trials got infected with COVID-19 after being administered with the vaccine. The high efficacy of the vaccine was confirmed by high precision tests for antibodies in the blood serum of volunteers (including an analysis for antibodies that neutralize the coronavirus), as well as the ability of the immune cells of the volunteers to activate in response to the spike S protein of the coronavirus, which indicates the formation of both antibody and cellular immune vaccine response.

Phase 3 clinical trial involving more than 2,000 people in Russia, a number of Middle Eastern (UAE and Saudi Arabia), and Latin American countries (Brazil and Mexico) will start on August 12.

Russia has released no scientific data on its testing and experts are unable to verify the vaccine’s claimed safety or effectiveness.

Status: On August 28, 2020, the trial was registered for Phase 3 – 40,000 participants, limited outcome measures, including adults with no upper age restriction, to be conducted in Russia.

NCT04436471 and NCT04437875: Two open, non-randomised phase 1/2 studies at two hospitals in Russia (76 participants to the two studies) – A heterologous COVID-19 vaccine consisting of two components, a recombinant adenovirus type 26 (rAd26) vector and a recombinant adenovirus type 5 (rAd5) vector, both carrying the gene for SARS-CoV-2 spike glycoprotein (rAd26-S and rAd5-S). The heterologous rAd26 and rAd5 vector-based COVID-19 vaccine has a good safety profile and induced strong humoral and cellular immune responses in participants.

References:

  • Sputnik Vaccine official website.
  • Publication: Safety and immunogenicity of an rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine in two formulations: two open, non-randomised phase 1/2 studies from Russia. Lancet (09/04/20).
  • News: The first batch of the Sputnik V coronavirus vaccine released into civil circulation Ministry of Health of the Russian Federation (09/08/20).

Candidate: Recombinant Protein Vaccine formulation 1 or 2 with adjuvant 1 or 2, or without adjuvant.

Sponsors/Developers: Sanofi Pasteur, GlaxoSmithKline.

Location: United States.

Trial Identifier: NCT04537208 (Phase 1/2)

Description: Pre-clinical studies showed promising safety and immunogenicity. The Phase 1/2 clinical trial is a randomised, double blind and placebo-controlled trial designed to evaluate the safety, reactogenicity (tolerability) and immunogenicity (immune response) of the COVID-19 vaccine candidate. A total of 440 healthy adults are being enrolled in the trial across 11 investigational sites in the United States. Pending positive Phase 1/2 data, companies aim to move into Phase 3 by end of 2020. The Companies anticipate first results in early December 2020, to support the initiation of a Phase 3 trial in December 2020.  If these data are sufficient for licensure application, it is planned to request regulatory approval in the first half of 2021. Sanofi and GSK are scaling up manufacturing of the antigen and adjuvant with the target of producing up to one billion doses in 2021.

Status: The partners plan to supply a significant portion of total worldwide available supply in 2021/2022 to COVAX, the vaccines pillar of the ACT-Accelerator (Access to COVID‐19 Tools), a global collaboration of leaders of governments, global health organisations, businesses and philanthropies to accelerate development, production, and equitable access to COVID-19 tests, treatments, and vaccines.

References:

  • Press Relase: Sanofi and GSK initiate Phase 1/2 clinical trial of COVID-19 adjuvanted recombinant protein-based vaccine candidate (09/03/20).
  • Press Release: Sanofi and GSK to join forces in unprecedented vaccine collaboration to fight COVID-19 (04/14/20).

Candidate: Non-replicating viral vector (Adenovirus type 5 vector) vaccine

Sponsors/Developers: CanSino Biologics | Beijing Institute of Biotechnology (Beijing); Jiangsu Province CDC, Hubei Provincial CDC, Zhongnan Hospital, Canadian Center for Vaccinology

Location: China, Canada, Pakistan

Trial identifier: LIMITED APPROVAL (Military use only). NCT04313127 (Phase 1), NCT04398147 (Phase 2, Canada), NCT04341389 (Phase 2, China), NCT04526990 (Phase 3, Pakistan)

Description: Recombinant adenovirus type 5 (Ad5) vector expressing the SARS-CoV-2 S protein: The vaccine is a replication defective Ad5 vectored vaccine expressing the spike glycoprotein of SARS-CoV-2. An optimised full-length spike gene based on Wuhan-Hu-1 (GenBank accession number YP_009724390) was cloned with the tissue plasminogen activator signal peptide gene into an E1 and E3 deleted Ad5 vector and constructed the Ad5 vectored COVID-19 vaccine using the Admax system from Microbix Biosystem (Toronto, ON, Canada). The Ad5 vectored COVID-19 vaccine was manufactured as a liquid formulation containing 5×1010 viral particles per 0.5 mL in a vial.

On Monday, June 29, the company developing a vaccine called Ad5-nCoV, CanSino, announced it had been authorized for use in the military by the country’s Central Military Commission. On 20 July 2020, results were published for the randomized, double-blind, placebo-controlled, phase 2 trial of the candidate non-replicating adenovirus type-5 (Ad5)-vectored COVID-19 vaccine was done in a single center in Wuhan, China (ClinicalTrials.gov, NCT04341389). 508 participants were randomly assigned to receive the vaccine (1x10E11 viral particles n=253; 5x10E11 viral particles n=129) or placebo (n=126). Both doses of the vaccine induced significant neutralizing antibody responses to live SARS-CoV-2. Specific interferon gamma enzyme-linked immunospot assay responses post vaccination was observed in 227 (90%) and 113 (88%) of viral particles dose groups. Severe adverse reactions were observed in 24 (9%) participants and one (1%) participant respectively.

CanSino’s Phase 3 trial was registered on 26 August 2020, with 40000 target participants, centered out of Pakistan. On August 20, another phase 3 trial was announced by CanSino: 10,000 participants this time. This is in addition to the 5000 in Saudi Arabia, 625 in Russia and unknown number in Mexico: their goal was 40000.

Status: The Phase III trial of the Ad5-nCoV vaccine candidate has been launched in Moscow, following health ministry authorization. CanSino will work with NPO Petrovax Pharm to conduct the trials in Russia. The Russian approval comes after CanSino and the National Research Council (NRC) of Canada terminated their collaboration on the development of the vaccine. CanSino plans to test its vaccine candidate in multiple countries globally.

References:

  • Publication: Safety, tolerability, and immunogenicity of a recombinant adenovirus type-5 vectored COVID-19 vaccine: a dose-escalation, open-label, non-randomised, first-in-human trial The Lancet (06/13/20).
  • Preprint: A single dose of an adenovirus-vectored vaccine provides complete protection of the upper and lower respiratory tracts against SARS-CoV-2 challenge (06/18/20).
  • Publication: Immunogenicity and safety of a recombinant adenovirus type-5-vectored COVID-19 vaccine in healthy adults aged 18 years or older: a randomised, double-blind, placebo-controlled, phase 2 trial. The Lancet. (07/20/20).
  • News: CanSino has its 1st phase 3 trial Covid-19 vaccine partner (Saudi Arabia & 5,000 people) (08/10/20).
  • Publication: A single dose of an adenovirus-vectored vaccine provides protection against SARS-CoV-2 challenge. Nature (08/14/20).
  • News: Pakistan gives go-ahead to Phase 3 COVID-19 vaccine trial (08/20/20).
  • News: Russia approves Phase III trial of CanSino’s Covid-19 vaccine (09/02/20).

Updated: 25 November, 2020.

Table: Summary of all vaccine candidates under evaluation – 44 clinical and 153 pre-clinical (as of October 28, 2020).

  • A monoclonal antibody against staphylococcal enterotoxin B superantigen inhibits SARS-CoV-2 entry in vitro [Link] (11/25/20)
  • Regeneron’s casirivimab and imdevimab antibody cocktail for COVID-19 is first combination therapy to receive FDA emergency use authorization [Link] (11/25/20)
  • Tocilizumab effective in treating sickest COVID-19 patients [Link] (11/20/20)
  • The Development of a Novel Nanobody Therapeutic for SARS-CoV-2 [Link] (11/20/20)
  • Sorrento Announces IND Filing for COVI-DROPS, an Intranasal Formulation of a High Potency Neutralizing Antibody Against SARS-CoV-2 [Link] (11/20/20)
  • Highly potent bispecific sybodies neutralize SARS-CoV-2  [Link] (11/18/20)
  • Can a nose-full of chicken antibodies ward off coronavirus infections?  [Link] (11/13/20)
  • Lilly’s neutralizing antibody bamlanivimab (LY-CoV555) receives FDA emergency use authorization for the treatment of recently diagnosed COVID-19  [Link] (11/13/20)
  • Humanized COVID‐19 decoy antibody effectively blocks viral entry and prevents SARS‐CoV‐2 infection  [Link] (11/13/20)
  • Humanigen Announces Positive Interim Phase 3 Data of Lenzilumab in Patients Hospitalized with COVID-19 [Link] (11/13/20)
  • Clinical Characteristics and Outcomes of COVID-19 Patients Receiving Compassionate Use Leronlimab [Link] (11/13/20)
  • An ultrapotent synthetic nanobody neutralizes SARS-CoV-2 by stabilizing inactive Spike, retains function after aerosolization, lyophilization, and heat treatment [Link] (11/06/20)
  • Study finds no evidence for efficacy of tocilizumab administration on mortality in severe COVID-19 [Link] (11/06/20)
  • Nanobodies from a synthetic library, known as sybodies, that target the receptor-binding domain of Spike protein shows low nanomolar binding affinities and efficient neutralization activity [Link] (11/06/20)
  • Results published for Lilly’s bamlanivimab (LY-CoV555) Phase 2 BLAZE-1 study show benefits for 700 mg dose in mild to moderate COVID-19 [Link] (11/04/20)
  • Early tocilizumab dosing is associated with improved survival in 118 patients who required mechanical ventilation [Link] (11/04/20)
  • Additional data from 524 patients in Phase 2/3 trial for Regeneron’s antibody cocktail REGN-COV2 provides definitive final virology results and meets the clinical endpoint [Link] (11/04/20)

Monoclonal antibodies provide an alternative avenue for the prevention of COVID-19, as the vaccine development process can take at least 12-18 months. Neutralizing mAbs to SARS-CoV-2 have the potential for both therapeutic and prophylactic applications and can help to guide vaccine design and development. Numerous research groups have isolated mAbs (most often from the B cells of patients who have recently recovered from SARS-CoV-2, and in some cases from individuals who were infected with SARS-CoV in 2003). It is also possible to generate effective mAbs by immunization of humanized mice. Modern methods allow the rapid identification of pathogen-specific B cells and recovery of immunoglobulin heavy chain and light chain genes that can be expressed to produce mAbs, usually in the form of IgG. The main target of SARS-CoV-2 neutralizing mAbs is the surface spike glycoprotein that mediates viral entry into host cells. Essentially all mAbs of interest target this protein. Viral infection is mediated by the interaction between the viral spike and the angiotensin-converting enzyme 2 (ACE 2) receptor found on numerous cell types, but neutralizing mAbs block this event. Immune system of nearly everyone who recovers from COVID-19 produces antibodies against SARS-CoV-2, the novel coronavirus that causes this easily transmitted respiratory disease. mAbs are currently used to treat a variety of conditions, including asthma, cancer, Crohn’s disease, and rheumatoid arthritis. One advantage of this class of therapeutics is that the timelines for their development, testing, and approval are typically shorter than those for drugs made of chemical compounds, called small molecules. Because of these and other factors, many experts think antibody-based therapies may offer one of the best near-term options for developing safe, effective treatments for COVID-19 [1].


Select strategies are detailed in the section below:

Candidate: COV2-2196 and COV2-2130, AZD7442 (AZD8895 + AZD1061)

Developers: Astrazeneca, Vanderbilt University Medical Center, Parexel

Locations: United Kingdom

Clinical Trial IDs: NCT04507256 (Phase 1)

Description: AZD7442 is a combination of two mAbs derived from convalescent patients with SARS-CoV-2 infection. Discovered by Vanderbilt University Medical Center and licensed to AstraZeneca in June 2020, the mAbs were optimized by AstraZeneca with half-life extension and reduced Fc receptor binding. The half-life extended mAbs should afford at least six months of protection from COVID-19. The mAbs were shown preclinically to block the binding of the SARS-CoV-2 virus to host cells and protect against infection in cell and animal models of disease. The two potently neutralizing monoclonal antibodies, COV2-2196 and COV2-2130, which recognize non-overlapping sites, bound simultaneously to the S protein and neutralized wild-type SARS-CoV-2 virus in a synergistic manner.

On August 25, AstraZeneca began Phase 1 trial for mAbs combination. The trial will evaluate the safety, tolerability and pharmacokinetics of AZD7442. The trial will include up to 48 healthy participants in the UK aged 18 to 55 years and is funded by the Defense Advanced Research Projects Agency (DARPA), part of the US Department of Defense, and the Biomedical Advanced Research and Development Authority (BARDA), part of the Office of the Assistant Secretary for Preparedness and Response at the US Department of Health and Human Services.

Status: Two trials of AZD7442 will enrol over 6,000 adults for the prevention of COVID-19 with additional trials enrolling ~4,000 adults for the treatment of SARS-CoV-2 infections. US Government is set to invest ~$486m for development and supply of up to 100,000 doses and can acquire another one million doses.

References:

  • Press Release: Vanderbilt, AstraZeneca collaborate on new COVID-19 antibody research. Astrazeneca (06/09/20).
  • Publication: Potently neutralizing and protective human antibodies against SARS-CoV-2. Nature (07/15/20).
  • Press Release: Phase I clinical trial initiated for monoclonal antibody combination for the prevention and treatment of COVID-19. Astrazeneca (08/25/20).
  • Press Release: COVID-19 Long-Acting AntiBody (LAAB) combination AZD7442 rapidly advances into Phase III clinical trials. AstraZeneca (10/09/20).

Candidate: LY3819253 (Bamlanivimab, LY-CoV555) and LY3832479 (Etesevimab, LY-CoV016, JS016); Mono- and Combination thearapies.

Developers: Eli Lilly, AbCellera, Shanghai Junshi Biosciences, NIAID.

Locations: United States.

Clinical Trial IDs: NCT04441931 (Phase 1), NCT04411628 (Phase 1), BLAZE-2/NCT04497987 (Phase 3), BLAZE-1/NCT04427501 (Phase 2)

Description: LY-CoV555 is a potent, neutralizing IgG1 mAb directed against the spike protein of SARS-CoV-2. It is designed to block viral attachment and entry into human cells, thus neutralizing the virus, potentially preventing and treating COVID-19. Emerged from the collaboration between Lilly and AbCellera to create antibody therapies for the prevention and treatment of COVID-19. Lilly scientists rapidly developed the antibody in less than three months after it was discovered by AbCellera and tested by the scientists at the National Institute of Allergy and Infectious Diseases (NIAID) Vaccine Research Center. It was identified from a blood sample taken from one of the first U.S. patients who recovered from COVID-19.

LY-CoV016 (also known as JS016) is a recombinant fully human monoclonal neutralizing antibody, which specifically binds to the SARS-CoV-2 surface spike protein receptor binding domain with high affinity and can effectively block the binding of the virus to the ACE2 host cell surface receptor. Point mutations were introduced into the native human IgG1 antibody to mitigate effector function. A SARS-CoV-2 challenge study was conducted in rhesus macaques and showed LY-CoV016 is effective for both prophylactic and therapeutic venues against SARS-CoV-2 infection.

Lilly has successfully completed enrollment and primary safety assessments of LY-CoV555 in a Phase 1 study of hospitalized patients with COVID-19 (NCT04411628) and long-term follow-up is ongoing. Lilly has also successfully completed a Phase 1 study (NCT04441931) of LY-CoV016 in healthy U.S. volunteers to evaluate the safety, tolerability, pharmacokinetics and immunogenicity. LY-CoV016 has been well tolerated and no drug-related severe adverse events (SAEs) have been observed to date.

Preprint on Eli Lilly’s candidate mAb reported that high-throughput microfluidic screening of antigen-specific B-cells led to the identification of LY-CoV555, a potent anti-spike neutralizing antibody from a convalescent COVID-19 patient. Biochemical, structural, and functional characterization revealed high-affinity binding to the receptor-binding domain, ACE2 binding inhibition, and potent neutralizing activity. In a rhesus macaque challenge model, prophylaxis doses as low as 2.5 mg/kg reduced viral replication in the upper and lower respiratory tract.

Status: On October 7, 2020, Lilly announced that it has submitted request for emergency use authorization (EUA) for monotherapy to U.S. FDA. New data show combination therapy met primary and secondary endpoints, reducing viral load, symptoms and hospitalizations. Lilly also plans to initiate a large open-label pragmatic study in COVID-19 outpatients in October.

In LY-CoV555 monotherapy studies there have been isolated drug-related infusion reactions or hypersensitivity that were generally mild (two reported as serious infusion reactions, all patients recovered). Treatment emergent adverse events were comparable to placebo for both LY-CoV555 monotherapy and combination therapy.

Combination therapy – Data from a new interim analysis of the BLAZE-1 (NCT04427501) clinical trial showed that combination therapy with two of Lilly’s SARS-CoV-2 neutralizing antibodies reduced viral load, symptoms and COVID-related hospitalization and ER visits. The randomized, double-blind, placebo-controlled Phase 2 study evaluated LY-CoV555 and LY-CoV016, which bind complementary regions of the SARS-CoV-2 spike protein, for the treatment of symptomatic COVID-19 in the outpatient setting. The combination cohort enrolled recently diagnosed patients with mild-to-moderate COVID-19, who were assigned to 2800 mg of each antibody (n=112) or placebo (n=156). The combination therapy significantly reduced viral load at day 11 (p=0.011), meeting the primary endpoint of the study. Most patients, including those receiving placebo, demonstrated near complete viral clearance by day 11. Combination therapy has been generally well tolerated with no drug-related serious adverse events. The BLAZE-1 clinical trial continues to enroll a confirmatory cohort of higher-risk patients who have been recently diagnosed with mild-to-moderate COVID-19.

Other ongoing clinical trials include a Phase 3 study of LY-CoV555 monotherapy for the prevention of COVID-19 in residents and staff at long-term care facilities (BLAZE-2, NCT04497987). In addition, LY-CoV555 monotherapy is being tested in the National Institutes of Health-led ACTIV-2 and ACTIV-3 studies of ambulatory and hospitalized COVID-19 patients.

References:

  • Press Release: Lilly Begins World’s First Study of a Potential COVID-19 Antibody Treatment in Humans. Eli Lilly (06/01/20).
  • Press Release: Lilly Initiates Phase 3 Trial of LY-CoV555 for Prevention of COVID-19 at Long-Term Care Facilities in Partnership with the National Institute of Allergy and Infectious Diseases (NIAID). Eli Lilly (08/03/20).
  • Press Release: Lilly announces proof of concept data for neutralizing antibody LY-CoV555 in the COVID-19 outpatient setting. Eli Lilly (09/16/20).
  • Preprint: LY-CoV555, a rapidly isolated potent neutralizing antibody, provides protection in a non-human primate model of SARS-CoV-2 infection. bioRxiv (10/01/20).
  • Press Release: Lilly provides comprehensive update on progress of SARS-CoV-2 neutralizing antibody programs. Eli Lilly (10/07/20).

Candidate: Adalimumab (Humira)

Developers: AbbVie Inc., University of Oxford

Locations: United Kingdom; China

Clinical Trial IDs: ISRCTN33260034 (Phase 2)

Description: Adalimumab is a human recombinant monoclonal antibody directed against the soluble and cell-bound forms of tumor necrosis factor-alpha and has been used for inflammatory conditions. It is approved for use in rheumatoid arthritis, juvenile idiopathic arthritis, ankylosing spondylitis, inflammatory bowel disease, and both the skin and joint manifestations of psoriasis. Recent studies have shown that COVID-19 patients taking anti-TNF drugs are less likely to be hospitalized, the university said.

Data from SECURE-IBD, a coronavirus and IBD database, have shown that of 116 patients on anti-TNF therapy who contracted Covid-19, 99 recovered without hospitalization and one patient died. Meanwhile, in 71 patients who were receiving only 5-aminosalicylates for their underlying inflammatory disease, half recovered without hospitalization and six patients died. This suggests that IBD patients with Covid-19 receiving anti-TNF therapy do not fare worse than those treated with other therapies.

Status: On September 30, 2020, researchers at the University of Oxford announced the start of a new study to explore the effectiveness of the adalimumab as a treatment for patients with COVID-19 in the community, especially care homes. The AVID-CC trial, which will be conducted by Oxford Clinical Trials Research Unit (OCTRU), will enroll up to 750 patients from community care settings throughout the UK.

It is funded by the COVID-19 Therapeutics Accelerator, an initiative set up by Wellcome, the Bill and Melinda Gates Foundation and Mastercard, with support from an array of public and philanthropic donors.

“The observed potential of anti-TNF drugs has prompted us to conduct a study in patients in community care to see whether treatment with the anti-TNF drug adalimumab reduces the progression to severe or critical disease or death in COVID-19 patients,” said Prof Duncan Richards, Professor of Clinical Therapeutics, University of Oxford.

References:

  • Press Release: Oxford researchers start new trial on the use of anti-TNF to treat Covid-19 in care homes. University of Oxford (09/30/20).
  • News: Anti-TNF therapy could treat patients suffering from Covid-19-related ARDS (05/29/20).
  • Trial Page: Adalimumab for coronavirus in community care. OCTRU (09/30/20).

Candidate: VIR-7831 and VIR-7832

Developers: Vir Biotechnology, GlaxoSmithKline

Locations: United States

Clinical Trial IDs: NCT04545060 (Phase 2/3)

Description: VIR-7831 is a monoclonal antibody that has demonstrated the ability to neutralize SARS-CoV-2 live virus in vitro. The antibody binds to an epitope on SARS-CoV-2 that is shared with SARS-CoV-1 (also known as SARS), indicating that the epitope is highly conserved, which may make it more difficult for escape mutants to develop. VIR-7831 has been engineered to enhance bioavailability and have an extended half-life.

VIR-7832 is a monoclonal antibody that has demonstrated the ability to neutralize SARS-CoV-2 live virus in vitro. The antibody binds to an epitope on SARS-CoV-2 that is shared with SARS-CoV-1 (also known as SARS), indicating that the epitope is highly conserved, which may make it more difficult for escape mutants to develop. VIR-7832 has been engineered to enhance bioavailability, have an extended half-life and to potentially function as a T cell vaccine.

On August 31, 2020, Vir Biotechnology and GSK announced start of Phase 2/3 study of the antibody treatment. The first patient was dosed last week in a Phase 2/3 study with VIR-7831 (also known as GSK4182136), a fully human anti-SARS-CoV-2 monoclonal antibody, for the early treatment of COVID-19 in patients who are at high risk of hospitalization. The aim of the COMET-ICE (COVID-19 Monoclonal antibody Efficacy Trial – Intent to Care Early) study, which will enroll approximately 1,300 patients worldwide who have early symptomatic infection, is to assess whether VIR-7831, as a single-dose monoclonal antibody, can prevent hospitalization due to COVID-19. Initial results may be available before the end of this year.

Status: Vir Biotechnology is expanding its Phase III COMET-ICE study evaluating VIR-7831 for the early treatment of COVID-19 in patients who are at high risk of hospitalization.

References:

  • Website: Vir Bio’s antibody pipeline (accessed 09/21/20).
  • Press release: GSK and Vir Biotechnology enter collaboration to find coronavirus solutions (04/06/21).
  • Press Release: Vir Biotechnology and GSK Start Phase 2/3 Study of COVID-19 Antibody Treatment. Vir Biotechnology (09/14/20).
  • Press Release: Vir Biotechnology and GSK announce global expansion to Phase 3 of COMET-ICE study evaluating VIR-7831 for the treatment of COVID-19. Vir Bio (10/06/20).

Candidate: Tocilizumab (Actemra/RoActemra)

Developers: Roche, Genentech

Locations: USA, Canada, Denmark, France, Germany, Italy, Netherlands, Spain, UK.

Clinical Trial IDs: COVACTA/NCT04320615 (phase III), REMDACTA/NCT04409262 (phase III), EMPACTA/NCT04372186 (phase III)

Description: Actemra/RoActemra was the first approved anti-IL-6 receptor biologic available in both intravenous and subcutaneous formulations for the treatment of adult patients with moderate-to-severe active rheumatoid arthritis. On 19 March, Roche announced the initiation of COVACTA- a clinical trial to evaluate the safety and efficacy of intravenous Actemra/RoActemra (tocilizumab) plus SoC in hospitalised adult patients with severe COVID-19 pneumonia compared to placebo plus SoC. COVACTA is a double-blind, placebo-controlled phase III study in approximately 450 adult patients hospitalised with severe COVID-19 pneumonia. REMDACTA is a two-armed global phase III, randomised, double-blind, multicentre study to evaluate the efficacy and safety of Actemra/RoActemra plus remdesivir, versus placebo plus remdesivir in hospitalised patients with severe COVID-19 pneumonia receiving Soc.

Genentech’s EMPACTA will evaluate the efficacy and safety of tocilizumab (TCZ) compared with a placebo in combination with standard of care (SOC) in hospitalized participants with COVID-19 pneumonia. EMPACTA is the first global Phase III trial with a focus on enrolling largely underserved and minority patients.

On July 29, 2020, Roche announced that the trial did not meet its primary endpoint of improved clinical status in patients with COVID-19 associated pneumonia, or the key secondary endpoint of reduced patient mortality. The study was the first global, randomised, double-blind, placebo-controlled phase III trial investigating in this setting. Roche remains committed to continuing the clinical trial program to further explore Actemra/RoActemra in other treatment settings, including in combination with an antiviral.

Status: In a preprint published September 12, 2020, authors reported that the COVACTA trial (NCT04320615) in hospitalized COVID-19 pneumonia patients (Overall 452 – 94 tocilizumab-treated and 144 placebo-treated), tocilizumab did not improve clinical status or mortality. Potential benefits in time to hospital discharge and duration of ICU stay are being investigated in ongoing clinical trials.

On September 17, 2020, EMPACTA became the first global Phase III trial to show efficacy with Actemra in COVID-19 associated pneumonia. There was no statistical difference in mortality between patients who received Actemra or placebo. The cumulative proportion of patients who progressed to mechanical ventilation or death by day 28 was 12.2% in the Actemra/RoActemra arm versus 19.3% in the placebo arm. The EMPACTA study did not identify any new safety signals for Actemra/RoActemra. Approximately 85% of the 389 patients were from minority racial and ethnic groups.

References:

  • Publication: Subcutaneous tocilizumab treatment in patients with severe COVID-19–related cytokine release syndrome: An observational cohort study. The Lancet (07/01/20).
  • Press Release: Roche provides an update on the phase III COVACTA trial of Actemra/RoActemra in hospitalised patients with severe COVID-19 associated pneumonia. Roche (07/29/20).
  • Preprint: Tocilizumab in Hospitalized Patients With COVID-19 Pneumonia. medRxiv (9/12/20).
  • Press Release: Genentech’s Phase III EMPACTA Study Showed Actemra Reduced the Likelihood of Needing Mechanical Ventilation in Hospitalized Patients With COVID-19 Associated Pneumonia. Genentech (9/17/20).

Candidate: Lenzilumab

Developers: Humanigen

Locations: United States

Clinical Trial IDs: NCT04351152 (Phase 3)

Description: Lenzilumab is a first-in-class Humaneered recombinant mAB targeting human GM-CSF, with potential immunomodulatory activity, high binding affinity in the picomolar range, 94% homology to human germline, and has low immunogenicity. Following intravenous administration, lenzilumab binds to and neutralizes GM-CSF, preventing GM-CSF binding to its receptor, thereby preventing GM-CSF-mediated signaling to myeloid progenitor cells. Lenzilumab has been studied across 4 completed clinical trials in healthy volunteers, and persons with asthma, rheumatoid arthritis, and chronic myelomonocytic leukemia.  A total of 113 individuals received lenzilumab in these trials; lenzilumab was very well tolerated with a low frequency and severity of adverse events.  

Lenzilumab has been shown to have a protective effect against cytokine release syndrome associated with CAR-T therapy. It’s believed that Lenzilumab can aid cytokine-mediated immunopathology of lung injury and ARDS.

Early results from the first 12 patients who received lenzilumab at Mayo Clinic locations showed 11 of 12 patients (92%) had clinical improvement, with a median discharge time of 5 days. Oxygenation was also improved in patients taking lenzilumab.

Humanigen now expects to complete enrolment of the 300 subjects this month with topline results due in the fourth quarter. Statements regarding the potential that lenzilumab will receive an Emergency Use Authorization in 2020 and commence commercialization, and regarding the potential additional manufacturing capacity afforded by the collaboration beginning in 2021.

On September 1, 2020, Lenzilumab is being evaluated in an ongoing Phase III trial and was selected by the NIH for its COVID-19 Big Effect Trial. 80% reduction in relative risk of invasive mechanical ventilation and/or death in patients treated with lenzilumab compared to the control group. Median time to resolution of acute respiratory distress syndrome (ARDS) reduced to one day for patients treated with lenzilumab versus eight days in control group. Lenzilumab patients discharged from the hospital in less than half the time compared with control group. The study involved a total of 39 patients, including 12 treated with lenzilumab, and 27 contemporaneous matched control patients who received standard of care treatment.

Status: A case report shared by Humanigen on October 06, demonstrated rapid resolution of hypoxemia and mobility and potential benefit of lenzilumab beyond the initial acute hyper-inflammatory window. After 13 weeks of hospitalization, administration of lenzilumab resulted in rapid improvement in oxygenation and subsequent discharge.

References:

  • Preprint: First Clinical Use of Lenzilumab to Neutralize GM-CSF in Patients with Severe COVID-19 Pneumonia. medRxiv (14/06/20).
  • Press Release Humanigen Expands Phase III Study of Lenzilumab in COVID-19 to Brazil (10/08/2020).
  • Press Release: Humanigen Reports Additional Analysis of Lenzilumab in Severe and Critical COVID-19 Patients Humanigen (16/06/2020).
  • Press Release: Lenzilumab COVID-19 Case-Control Study Published in Mayo Clinic Journal. Humanigen (01/09/2020).
  • Press Release: Humanigen says review of lenzilumab Phase 3 study of COVID-19 by data safety monitoring board gets green light to continue. Humanigen (14/09/20).
  • Press Release: Humanigen and Lonza Announce Collaboration to Expand Manufacturing of Humanigen’s COVID-19 Therapeutic Candidate Lenzilumab. Humanigen (15/09/20).
  • Press Release: Humanigen Announces COVID-19 Case Report Demonstrating Rapid Resolution and Discharge after Single IND Emergency Use Authorization of Lenzilumab. Humanigen (10/06/20).

Candidate: REGN10933 and REGN10987

Developers: Regeneron Pharmaceuticals

Locations: United States

Clinical Trial IDs: NCT04425629 (Phase 1), NCT04426695 (Phase 1), NCT04519437 (Phase 1)

Description: REGN-COV2 comprises two mABs (REGN10933 and REGN10987) and was designed specifically by Regeneron scientists to block infectivity of SARS-CoV-2, the virus that causes COVID-19. Regeneron scientists evaluated thousands of fully-human antibodies produced by the company’s proprietary VelocImmunemice, which have been genetically-modified to have a human immune system, as well as antibodies isolated from humans who have recovered from COVID-19. They selected the two most potent, non-competing and virus-neutralizing antibodies to create REGN-COV2 and have scaled up this dual-antibody cocktail for clinical use with the company’s in-house VelociMaband manufacturing capabilities. REGN-COV2’s two antibodies bind non-competitively to the critical receptor binding domain of the virus’s spike protein, which diminishes the ability of mutant viruses to escape treatment and protects against spike variants that have arisen in the human population.

Regeneron announced the initiation of  Phase 3 trial will evaluate REGN-COV2’s ability to prevent infection among uninfected people who have had close exposure to a COVID-19 patient (such as the patient’s housemate), and is being run jointly with the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH). REGN-COV2 has also moved into the Phase 2/3 portion of two adaptive Phase 1/2/3 trials testing the cocktail’s ability to treat hospitalized and non-hospitalized (or “ambulatory”) patients with COVID-19. This clinical progress follows a positive review from the Independent Data Monitoring Committee of REGN-COV2 Phase 1 safety results in an initial cohort of 30 hospitalized and non-hospitalized patients with COVID-19. The Phase 3 prevention trial is being conducted at approximately 100 sites and is expected to enroll 2,000 patients in the U.S.; the trial will assess SARS-CoV-2 infection status. The two Phase 2/3 treatment trials in hospitalized (estimated enrollment =1,850) and non-hospitalized (estimated enrollment =1,050) patients are planned to be conducted at approximately 150 sites in the U.S., Brazil, Mexico and Chile, and will evaluate virologic and clinical endpoints, with preliminary data expected later this summer. All trials are adaptively designed, and the ultimate numbers of patients enrolled will depend on trial progress and insights from Phase 2 studies.

Recent publication from Regeneron shows that REGN-COV2, greatly reduces virus load in lower and upper airway and decreases virus induced pathological sequalae when administered prophylactically or therapeutically in both rhesus macaques and golden hamsters. The ability of REGN-COV2 to almost completely block detection of sgRNA matches or exceeds the effects recently shown in vaccine efficacy studies.

On September 14, 2020, Regeneron Pharmaceuticals, and the University of Oxford announced that RECOVERY, one of the world’s largest randomized clinical trials of potential COVID-19 treatments, will evaluate Regeneron’s investigational anti-viral antibody cocktail, REGN-COV2. The Phase 3 open-label trial in patients hospitalized with COVID-19 will compare the effects of adding REGN-COV2 to the usual standard-of-care versus standard-of-care on its own. The open-label RECOVERY trial will assess the impact of adding REGN-COV2 to the usual standard-of-care on all-cause mortality 28 days after randomization. Other endpoints include the impact on hospital stay and the need for ventilation. It is anticipated that at least 2,000 patients will be randomly allocated to receive REGN-COV2 plus usual standard-of-care, and results will be compared with at least 2,000 patients who receive standard-of-care on its own. Usual standard-of-care varies by local hospital.

Status: Regeneron Pharmaceuticals on October 06 announced the first data from a descriptive analysis of a seamless Phase 1/2/3 trial of its investigational antibody cocktail REGN-COV2 showing it reduced viral load and the time to alleviate symptoms in non-hospitalized patients with COVID-19. REGN-COV2 also showed positive trends in reducing medical visits. The ongoing, randomized, double-blind trial measures the effect of adding REGN-COV2 to usual standard-of-care, compared to adding placebo to standard-of-care.

References:

  • Press Release: Phase III COVID-19 Prevention Trial with Antibody Cocktail. Regeneron (07/06/20).
  • Publication: Antibody cocktail to SARS-CoV-2 spike protein prevents rapid mutational escape seen with individual antibodies. Science (08/21/20).
  • Publication: Studies in humanized mice and convalescent humans yield a SARS-CoV-2 antibody cocktail. Science (08/21/20).
  • Preprint: REGN-COV2 antibody cocktail prevents and treats SARS-CoV-2 infection in rhesus macaques and hamsters. BioRxiv (08/03/20).
  • Press Release: Recovery covid-19 phase 3 trial to evaluate Regeneron’s REGN-COV2 investigational antibody cocktail in the UK. Regeneron (09/14/20).
  • Press Release: REGENERON’S REGN-COV2 ANTIBODY COCKTAIL REDUCED VIRAL LEVELS AND IMPROVED SYMPTOMS IN NON-HOSPITALIZED COVID-19 PATIENTS. Regeneron. (10/06/20).

Candidate: Sarilumab (Kevzara)

Developers: Sanofi, Regeneron Pharmaceuticals

Locations: Argentina, Brazil, Canada, Chile, France, Germany, Israel, Italy, Japan, Russian Federation, Spain

Clinical Trial IDs: NCT04327388 (Phase III); NCT04386239 (Phase 1)

Description: Kevzara is currently approved in multiple countries to treat adults with moderately to severely active rheumatoid arthritis who have not responded to or tolerated previous therapy. Kevzara is a fully-human mAB that inhibits the interleukin-6 (IL-6) pathway by binding and blocking the IL-6 receptor. IL-6 may play a role in driving the overactive inflammatory response in the lungs of patients who are severely or critically ill with COVID-19 infection. The role of IL-6 is supported by preliminary data from a single-arm study in China using another IL-6 receptor inhibitor.

U.S. Phase 3 trial of Kevzara (sarilumab) 400 mg in COVID-19 patients requiring mechanical ventilation did not meet its primary and key secondary endpoints when Kevzara was added to best supportive care compared to best supportive care alone (placebo). Minor positive trends were observed in the primary pre-specified analysis group (critical patients on Kevzara 400 mg who were mechanically ventilated at baseline) that did not reach statistical significance and these were countered by negative trends in a subgroup of critical patients who were not mechanically ventilated at baseline. A separate Sanofi-led trial outside of the U.S. in hospitalized patients with severe and critical COVID-19 using a different dosing regimen is ongoing.

Status: On September 1, Sanofi announced that the global Phase 3 trial investigating intravenously administered Kevzara (sarilumab) at a dose of 200 mg or 400 mg  in severely or critically ill  patients hospitalized with COVID-19 did not meet its primary endpoint and key secondary endpoint when Kevzara was compared to placebo added to usual hospital care. The 420-patient randomized trial was conducted outside the U.S. in Argentina, Brazil, Canada, Chile, France, Germany, Israel, Italy, Japan, Russia and Spain (86 in placebo, 161 in 200 mg, and 173 in 400 mg arms).

References:

  • Publication: COVID‐19 pneumonia treated with Sarilumab: A clinical series of eight patients. J Med Virol (06/16/20).
  • Preprint: Sarilumab use in severe SARS-CoV-2 pneumonia. medrxiv (05/18/20).
  • Press Release: Sanofi provides update on Kevzara® (sarilumab) Phase 3 trial in severe and critically ill COVID-19 patients outside the U.S. Sanofi (09/01/20).

Candidate: COVI-GUARD (Neutralizing Antibody – STI 1499) and COVI-SHIELD (Neutralizing Antibody Cocktail)

Developers: Sorrento Therapeutics, Inc.

Locations: United States

Clinical Trial IDs: NCT04454398 (Phase 1)

Description: Sorrento is developing a Neutralizing Antibody COVI-GUARD (Neutralizing Antibody – STI 1499) which binds to S1 subunit of SARS-CoV-2 Spike protein. It is also developing a Neutralizing Antibody Cocktail COVI-SHIELD (Neutralizing Antibody Cocktail)  to bind to distinct epitopes on SARS-CoV-2 Spike protein. The antibody cocktail potentially creates a high barrier to emergence of resistant variants in treated individuals. Both the mAbs Fc regions are engineered to eliminate interactions with host Fc receptors, thereby decreasing risk of Antibody Dependent Enhancement of SARS-CoV-2 infection.

Sorrento Therapeutics is teaming up with New York City-based Mount Sinai Health System to develop COVI-SHIELD to treat COVID-19. COVI-SHIELD is expected to deliver a mixture of three antibodies that combined recognize three specific regions of the SARS-CoV-2 Spike protein.

August 19, 2020, Sorrento announced that it is filing an investigational new drug application (IND) for COVI-GUARD (STI-1499) for hospitalized COVID-19 patients. Sorrento has previously received guidance from the FDA in response to a pre-IND meeting package and believes it has addressed all questions and followed the recommendations from the agency for all sections of the IND. As Sorrento previously announced, in preclinical studies, STI-1499 demonstrated 100% neutralizing effect (in vitro) of the antibody and that a low dose prevented SARS-CoV-2 from infecting healthy cells in such preclinical in vitro studies. Animal data generated by Dr. Paessler’s laboratory at the UTMB in Syrian Golden Hamsters infected with SARS-CoV-2, justify the IND filing and continued clinical development.

The highest proposed dose (200 mg per patient) in the phase 1 safety trial is a much lower dose than currently being tested for other known antibodies in active clinical studies. The potentially higher potency of the antibody may allow for faster scaled manufacturing (availability to patients) and potentially a lower cost per dose as compared to other known antibodies currently being evaluated.

STI-1499 antibody has also been evaluated in preclinical studies against multiple strains of SARS-CoV-2, including the highly contagious D614G mutant, the current dominant strain globally. In such preclinical studies, the antibody has been 100% effective against the highly contagious D614G mutant strain at a low dose.

On September 16, 2020, Sorrento announced that phase 1 clinical trial for STI-1499 (COVI-GUARD™) in hospitalized COVID-19 patients has received FDA notice that it may proceed with patient enrollment. The initial trial is expected to enroll rapidly and is expected to be followed by large trials targeting a potential EUA submission as early as before the end of this year. Sorrento has initiated cGMP manufacturing to produce 50,000 doses in anticipation of a potential EUA.

Status: On September 28, Sorrento released preclinical study results, both STI-1499 and STI-2020 demonstrated potent neutralizing activity against SARS-CoV-2 virus isolates, including the emerging Spike D614G variant virus. STI-1499 and STI-2020 also demonstrated protective activities against SARS-CoV-2 infection in Syrian golden hamsters. At day 5, STI-2020 at 500 ug reduced virus load in hamster lungs to undetectable levels in 100% of animals tested, whereas STI-1499 at 2,000 ug reduced virus load below the detection limit in 60% of animals tested and showed a 10-fold reduction in the remaining 40% of animals.

References:

  • Press Release: Sorrento And Mount Sinai Health System To Jointly Develop COVI-SHIELD™ Antibody Therapy Targeting SARS-CoV-2 Infection (COVID-19). Sorrento (05/12/2020).
  • Publication: Sorrento’s antibody completely blocks Covid-19 in-vitro. Pharmaceutical-technology (05/18/20).
  • Press Release: Sorrento Announces FDA IND Filing Today for COVI-GUARD Neutralizing and High Potency Antibody Against SARS-CoV-2. Sorrento (08/19/20).
  • Press Release: Sorrento Receives US FDA Clearance to Proceed With Phase 1 Clinical Trial of STI-1499 (COVI-GUARD) Neutralizing Antibody in COVID-19 Positive Patients. Sorrento (09/16/20).
  • Press Release: Sorrento Releases Preclinical Data for STI-1499 (COVI-Guard™) and STI-2020 (COVI-AMG™), Potent Neutralizing Antibodies Against SARS-CoV-2. Sorrento (09/28/20).

Updated: 25 November, 2020.

  • Ivermectin as an adjunct treatment for hospitalized adult COVID-19 patients: A randomized multi-center clinical trial [Link] (11/25/20)
  • Virtual screening of anti-HIV1 compounds against SARS-CoV-2: machine learning modeling, chemo-informatics and molecular dynamics simulation based analysis [Link] (11/25/20)
  • Peginterferon Lambda-1a for treatment of outpatients with uncomplicated COVID-19: a randomized placebo-controlled trial  [Link] (11/25/20)
  • Anti-COVID-19 efficacy of ivermectin in the golden hamster [Link] (11/25/20)
  • WHO recommends against the use of remdesivir in COVID-19 patients [Link] (11/25/20)
  • Remdesivir induced viral RNA and subgenomic RNA suppression, and evolution of viral variants in SARS-CoV-2 infected patients [Link] (11/25/20)
  • Efficacy and Safety of Favipiravir, an Oral RNA-Dependent RNA Polymerase Inhibitor, in Mild-to-Moderate COVID-19: A Randomized, Comparative, Open-Label, Multicenter, Phase 3 Clinical Trial [Link] (11/25/20)
  • UTHSC researchers identify three drugs as possible therapeutics for COVID-19 [Link] (11/20/20)
  • Synergistic Effect of Quercetin and Vitamin C Against COVID-19: Is a Possible Guard for Front Liners [Link] (11/20/20)
  • Quercetin and Its Metabolites Inhibit Recombinant Human Angiotensin-Converting Enzyme 2 (ACE2) Activity [Link] (11/20/20)
  • Chinese herbal compounds against SARS-CoV-2: puerarin and quercetin impair the binding of viral S-protein to ACE2 receptor [Link] (11/20/20)
  • Efficacy and Safety of Ivermectin for Treatment and prophylaxis of COVID-19 Pandemic  [Link] (11/18/20)
  • Baicalein inhibits SARS-CoV-2/VSV replication with interfering mitochondrial oxidative phosphorylation in a mPTP dependent manner [Link] (11/18/20)
  • Neuraminidase inhibitors rewire neutrophil function in murine sepsis and COVID-19 patient cells  [Link] (11/18/20)
  • Stenoparib, an inhibitor of cellular poly (ADP-ribose) polymerase (PARP), blocks replication of the SARS-CoV-2 human coronavirus in vitro [Link] (11/18/20)
  • Human soluble ACE2 improves the effect of remdesivir in SARS‐CoV‐2 infection [Link] (11/18/20)
  • Antiviral Effect of High-Dose Ivermectin in Adults with COVID-19: A Pilot Randomised, Controlled, Open Label, Multicentre Trial [Link] (11/13/20)
  • Remdesivir for 5 or 10 Days in Patients with Severe Covid-19 [Link] (11/13/20)
  • SARS-CoV-2 Mpro inhibitors: identification of anti-SARS-CoV-2 Mpro compounds from FDA approved drugs [Link] (11/13/20)
  • Early COVID-19 therapy with azithromycin plus nitazoxanide, ivermectin or hydroxychloroquine in outpatient settings significantly reduced symptoms compared to known outcomes in untreated patients [Link] (11/06/20)
  • Remdesivir-based therapy improved recovery of patients with COVID-19 in the SARSTer multicenter, real-world study [Link] (11/06/20)
  • Two natural substances with anti-inflammatory and anti-viral properties, Honey and Nigella sativa, cause significant reduction in the severity of disease, the time taken for viral clearance and mortality [Link] (11/06/20)
  • Two-dose ivermectin prophylaxis was associated 73% reduction of COVID-19 infection among healthcare workers for the following one-month [Link] (11/06/20)
  • Boceprevir, calpain inhibitors II and XII, and GC-376 show broad-spectrum antiviral activity in vitro and display synergic effect with remdesivir [Link] (11/04/20)
  • Protease inhibitor aprotinin displays anti-SARS-CoV-2 activity in different cell types [Link] (11/04/20)
  • Remdesivir metabolite GS-441524 effectively inhibits SARS-CoV-2 in human ACE2 transduced mice [Link] (11/04/20)

Select strategies are detailed in the section below:

Candidate: Remdesivir (Veklury, GS-5734)

Sponsors/Developers: Gilead Sciences, Inc.

Location: United States

Clinical Trial IDs: NCT04501952 (Outpatient Setting, Phase 3), NCT04431453 (CARAVAN, < 18 Years, Phase 2/3), NCT04292899 (Severe COVID-19, Phase 3), NCT04292730 (Moderate COVID-19, Phase 3), NCT04323761 (expanded access)

Description: The broad-spectrum antiviral agent Remdesivir (GS-5734; Gilead Sciences, Inc) is a nucleotide analog prodrug. The US FDA issued EUA of remdesivir to allow emergency use in children and hospitalized adults. The findings from the NIAID trial of remdesivir in hospitalized patients with advanced COVID-19 have been published in a peer-reviewed medical journal. These findings support the use of remdesivir in this population, with the largest benefit observed among individuals who required oxygen supplementation but were not mechanically ventilated. The open-label phase 3 SIMPLE trial (n = 397) in hospitalized patients with severe COVID-19 disease not requiring mechanical ventilation showed similar improvement in clinical status with the 5-day remdesivir regimen compared with the 10-day regimen on day 14 (OR=0.75). The first published report concerning remdesivir compassionate use described clinical improvement in 36 of 53 hospitalized patients (68%) with severe COVID-19. At baseline, 30 patients (57%) were receiving ventilation and 4 (8%) extracorporeal membrane oxygenation (ECMO).

Coordinating closely with the U.S. FDA, Gilead has designed and will soon begin enrollment of an open-label, single-arm Phase 2/3 clinical trial that will evaluate the safety, tolerability, pharmacokinetics and efficacy of remdesivir in treating approximately 50 pediatric patients with moderate-to-severe COVID-19, including newborns through adolescents. This important trial will be conducted at more than 30 sites in the United States and Europe (Trial ID: NCT04431453).

On July 10, 2020 Gilead presented additional data -Remdesivir was associated with an improvement in clinical recovery and a 62% reduction in the risk of mortality compared with standard of care – an important finding that requires confirmation in prospective clinical trials. Traditionally marginalized racial/ethnic groups treated with Remdesivir had similar clinical outcomes as overall patient population. Compassionate use program, which demonstrated that 83% of pediatric patients (n=77) and 92% of pregnant and postpartum women (n=86) with a broad spectrum of disease severity recovered by Day 28. To further the understanding of these results in individual patient cases, Gilead recently announced the initiation of a global, open-label Phase 2/3 trial to evaluate the safety, tolerability and pharmacokinetics of remdesivir in pediatric patients from birth to less than 18 years of age. Gilead is also collaborating on a study for pregnant women.

Status: Gilead announced on 28 August that the U.S. FDA expanded the Emergency Use Authorization (EUA) enabling use of the investigational antiviral Veklury (remdesivir) to treat all hospitalized patients with COVID-19, in addition to the previous authorization for patients hospitalized with severe COVID-19. The expanded EUA is based on results from the Phase 3 SIMPLE trial evaluating Veklury in hospitalized patients with moderate COVID-19 pneumonia, as well as results from the National Institute of Allergy and Infectious Diseases (NIAID) ACTT-1 trial in hospitalized patients with a range of disease severity.

Final results of the ACTT trial, presented in top-line form back in April, confirm that in patients hospitalized with COVID-19, remdesivir shortened the time to recovery from 15 days to 10 days compared with placebo. Mortality at days 15 and 29 was numerically lower with remdesivir.

References:

  • Publication: Remdesivir for the Treatment of Covid-19 – Preliminary Report. NEJM (05/22/20).
  • Publication: Remdesivir for 5 or 10 Days in Patients with Severe Covid-19. NEJM (05/27/20).
  • Publication: Clinical benefit of remdesivir in rhesus macaques infected with SARS-CoV-2. Nature (06/09/20).
  • Publication: Structural basis for inhibition of the RNA-dependent RNA polymerase from SARS-CoV-2 by remdesivir. Science (06/26/20).
  • Publication: Compassionate Use of Remdesivir for Patients with Severe Covid-19. NEJM (06/11/20).
  • Press Release: Gilead Presents Additional Data on Investigational Antiviral Remdesivir for the Treatment of COVID-19. Gilead (07/10/20).
  • Press Release: Gilead’s Investigational Antiviral Veklury® (Remdesivir) Receives U.S. Food and Drug Administration Emergency Use Authorization for the Treatment of Patients With Moderate COVID-19. Gilead (08/28/20).
  • Publication: Remdesivir for the Treatment of Covid-19 – Final Report. NEJM (10/08/20).

Candidate: Lopinavir-Ritonavir

Developers: University of Oxford

Locations: United Kingdom

Clinical Trial IDs: NCT04381936 – Randomised Evaluation of COVID-19 Therapy (RECOVERY)

Description: Lopinavir–ritonavir has been proposed as a treatment for COVID-19 on the basis of in vitro activity, preclinical studies, and observational studies. Lopinavir is a HIV-1 protease inhibitor, which is combined with ritonavir to increase its plasma half-life. Lopinavir is also an inhibitor of the severe acute respiratory syndrome coronavirus (SARS-CoV) main protease, which is critical for replication and appears to be highly conserved in SARS-CoV-2.

A previous randomised trial of lopinavir–ritonavir among 199 patients admitted to hospital with COVID-19 showed no improvement in viral load, duration of hospital stays, or mortality. The trial was too small to rule out the possibility of clinically relevant benefits and commentators recommended larger randomised trials to confirm or refute the lack of effect. RECOVERY trial is a randomised trial to assess whether lopinavir–ritonavir improves clinical outcomes in patients admitted to hospital with COVID-19.

Status: Full results of the lopinavir/ritonavir arm of the randomized, controlled, open-label RECOVERY trial has now been published in the Lancet. Top-line results released at the end of June concluded that there was no benefit to the medication, which is approved for use in HIV and had showed promise in vitro against SARS-CoV-2. Among more than 1,600 patients randomized to lopinavir/ritonavir and over 3,400 patients randomized to usual care, investigators saw no differences in death at 28 days across all subgroups, and no difference in time to hospital discharge or progression to mechanical ventilation or death. “Whilst it is disappointing that there was no significant benefit from lopinavir/ritonavir for patients in hospital, these findings have allowed us to focus our efforts on other promising treatments, and have informed the way in which individual patients are treated,” RECOVERY co-chief investigator Peter Horby, MBBS, PhD, said in a press statement. Of note, no signal of increased arrhythmia was seen with this combination agent.

References:

  • Publication: A Trial of Lopinavir–Ritonavir in Adults Hospitalized with Severe Covid-19. NEJM (05/07/20).
  • News: No clinical benefit from use of lopinavir-ritonavir in hospitalised COVID-19 patients studied in RECOVERY. University of Oxford (06/29/20).
  • Publication: Lopinavir–ritonavir in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial. The Lancet (10/05/20).

Candidate: Favipiravir (Avigan).

Sponsors/Developers: FUJIFILM Toyama Chemical Co., Ltd.

Location: United States, Japan, China, Middle East and other countries

Clinical Trial IDs: NCT04358549 (Phase 2), NCT04373733 (Phase 3)

Description: Favipiravir is an oral antiviral approved for the treatment of influenza in Japan. It selectively inhibits RNA polymerase, which is necessary for viral replication. Japan has commenced with a phase 3 clinical trial. In the United States, a phase 2 trial will enroll approximately 50 patients with COVID-19, in collaboration with Brigham and Women’s Hospital, Massachusetts General Hospital, and the University of Massachusetts Medical School. In India, a phase 3 trial combining 2 antiviral agents, favipiravir and umifenovir, started in May 2020.

Fujifilm will team up with India’s Dr. Reddy’s Laboratories to run a 1,000-person trial on flu med Avigan in coronavirus patients in Kuwait. The trial was originally slated to run in Japan, but low patient enrollment forced Fujifilm to relocate. In early July, Fujifilm granted Dr. Reddy’s a license to produce and sell Avigan as a potential COVID-19 treatment overseas in partnership with Global Response Aid.

Indian firm Glenmark’s open-label randomized, multicenter clinical trial conducted in 150 patients, evaluated the efficacy and safety of Favipiravir plus standard supportive care versus standard supportive care alone in mild to moderate patients, randomized within a 48 h window of testing RT-PCR positive for COVID-19. Results from the Phase 3 trial showed numerical improvements for the primary efficacy endpoint with 28.6%  faster viral clearance in the overall population as measured by the median time until cessation of oral shedding of virus in the Favipiravir treatment arm compared to those in the control arm (Hazard Ratio 1.367 [95%CI 0.944,1.979]; p=0.129). 40% faster achievement of “clinical cure” defined as the physician’s assessment with a statistically significant reduction in median time to clinical cure in the Favipiravir treatment arm (3 days vs. 5 days) [HR 1.749, p=0.029). No serious adverse events (SAEs) or deaths were observed.

FujiFilm, which has licensed GRA and Dr. Reddy’s to manufacture, distribute and sell the drug globally. Clinical trials of the drug have been conducted and are underway in the United States, Japan, China, the Middle East and other countries, where it is being used to reduce fevers and shorten recovery time in patients who receive Avigan in the early stages of infection with COVID-19. In July, the Central Drugs Standard Control Organisation of India’s Directorate General of Health Services approved Favipiravir for distribution, sale and use in treatment of COVID-19 patients.

Status: FUJIFILM  has announced that primary endpoint has been met in phase III clinical trial of “Avigan Tablet” conducted in Japan. The efficacy primary endpoint is time to negative conversion of detectable SARS-CoV 2 viral RNA in the RT-PCR assays, and to alleviation of symptoms (body temperature, oxygen saturation and chest images). FUJIFILM began a phase III clinical trial of Avigan in Japan in March 2020, for COVID-19 patients with non-severe pneumonia – a randomized, placebo-controlled, single-blind comparative study, to evaluate the efficacy and safety of Avigan. The median value of primary endpoints, using 156 individuals as analysis targets, were 11.9 days for the Avigan group and 14.7 days for the placebo group.

References:

  • Press Release: Fujifilm announces the start of a phase III clinical trial of influenza antiviral drug “Avigan Tablet” on COVID-19 and commits to increasing production. FUJIFILM (03/31/20).
  • Press Release: Fujifilm announces the start of a phase II clinical trial of its influenza antiviral drug “Avigan Tablet” for COVID-19 patients in the U.S. FUJIFILM (04/09/20).
  • News: Fujifilm to begin clinical trials testing Avigan in COVID-19 patients in Kuwait. Pharmafile (07/21/20).
  • Press Release: Glenmark Announces Top-Line Results From Phase 3 Clinical Trial of Favipiravir in Patients with Mild to Moderate COVID-19. Glenmark (07/22/20).
  • News: India Approves Avigan (Favipiravir) For COVID-19 Treatment. Business World (08/20/20).
  • Press Release: Anti-influenza drug Avigan Tablet Meets Primary Endpoint in Phase III Clinical Trial in Japan for COVID-19 patients. FUJIFILM (09/23/20).

There are no FDA-approved drugs for the treatment of COVID-19, although remdesivir, an investigational antiviral drug, is available through an FDA emergency use authorization. Definitive clinical trial data are needed to identify safe and effective treatments for COVID-19. COVID-19 Treatment Guidelines Panel provides recommendations on using antiviral drugs to treat COVID-19 based on the available data.

  • Remdesivir – For patients who do not require oxygen delivery through a high-flow device, noninvasive ventilation, invasive mechanical ventilation, or ECMO – The Panel recommends using remdesivir for 5 days or until hospital discharge, whichever comes first
  • The Panel recommends against the use of chloroquine or hydroxychloroquine or use of high-dose chloroquine (600 mg twice daily for 10 days) for the treatment of COVID-19, except in a clinical trial.
  • The Panel recommends against using combination of hydroxychloroquine plus azithromycin, because of the potential for toxicities.
  • The Panel recommends against using Lopinavir/ritonavir or other HIV protease inhibitors, because of unfavorable pharmacodynamics and because clinical trials have not demonstrated a clinical benefit.
  • The Panel recommends against the use of ivermectin for the treatment of COVID-19, except in a clinical trial

References:

  • NIH: Potential Antiviral Drugs Under Evaluation for the Treatment of COVID-19 (Accessed 09/21/20).

Candidate: EIDD-2801

Sponsors/Developers: Ridgeback Biotherapeutics, LP., Merck (MSD).

Location: United States, United Kingdom

Clinical Trial IDs: NCT04392219 (Phase 1), NCT04405739 (Phase 2), NCT04405570 (Phase 2)

Description: EIDD-2801 is an investigational, orally-bioavailable form of a potent ribonucleoside analog that inhibits the replication of multiple RNA viruses including SARS-CoV-2, the causative agent of COVID-19. In animal studies of two distinct coronaviruses (SARS-CoV-1 and MERS), EIDD-2801 has been shown to improve pulmonary function, decrease body-weight loss and reduce the amount of virus in the lung. EIDD-2801 was invented at Drug Innovations at Emory (DRIVE), LLC, a not-for-profit biotechnology company wholly owned by Emory University.

Under the agreement, announced on May 26, 2020, Merck (MSD), through a subsidiary, has acquired exclusive worldwide rights to develop EIDD-2801 and related molecules in collaboration with Ridgeback. Ridgeback will continue to fund and conduct multiple Ridgeback-sponsored Phase 1 and 2 trials and fund manufacturing campaigns for clinical supply. Going forward, the parties will collaborate on clinical development for COVID-19 and manufacturing, to be led by Merck. Consistent with the shared history and commitment to addressing global unmet needs in grievous illness, Merck and Ridgeback also plan to explore the potential for EIDD-2801 in other severe acute viral diseases, such as Ebola.

Status: Ridgeback Biotherapeutics announces the launch of two Phase 2 clinical trials to test the efficacy of EIDD-2801 as an anti-viral treatment for COVID-19. Phase 1 trials recently determined that EIDD-2801 is safe in human doses that provide blood levels well above levels that animal models suggest should be effective against SARS-CoV-2, the virus which causes COVID-19. EIDD-2801 will be administered to patients 18 years old and over in two studies: Study 2003 will enroll recently symptomatic, newly diagnosed patients in a home, or out of hospital, setting; Study 2004 will enroll hospitalized patients with COVID-19.

References:

  • Press Release: Ridgeback Biotherapeutics Announces Potential COVID-19 Treatment EIDD-2801 Will Leverage Innovative Testing Platform AGILE for Phase 2 Trial. BusinessWire (07/07/20).
  • Press Release: Ridgeback Biotherapeutics Announces Launch of Phase 2 Trials Testing EIDD-2801 as Potential Treatment. Ridgeback Biotherapeutics (06/19/20).
  • Press Release: Merck and Ridgeback Bio Announce Closing of Collaboration and Licensing Transaction. BusinessWire (07/01/20).

Candidate: Lopinavir/Ritonavir (Kaletra)

Sponsors/Developers: Multiple clinical trials

Location: Multiple locations

Clinical Trial IDs: NCT04330690 (Phase 2), Chinese Clinical Trial Register number ChiCTR2000029308

Description: Lopinavir/ritonavir is an inhibitor of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) 3CLpro in vitro, and this protease appears to be highly conserved in SARS-CoV-2. Although lopinavir/ritonavir has in vitro activity against SARS-CoV, it is thought to have a poor selectivity index, indicating that higher than tolerable levels of the drug might be required to achieve meaningful inhibition in vivo.

In a study published in NEJM on 5July 2020, treatment was not associated with a difference from standard care in the time to clinical improvement. A total of 199 patients with laboratory-confirmed SARS-CoV-2 infection participated in this randomized, controlled, open-label trial; 99 were assigned to the lopinavir-ritonavir group, and 100 to the standard-care group. Mortality at 28 days was similar in the lopinavir–ritonavir group and the standard-care group. Treatment was stopped early in 13 patients (13.8%) because of adverse events.

WHO on July 04, 2020, accepted the recommendation from the Solidarity Trial’s International Steering Committee to discontinue the trial’s hydroxychloroquine and lopinavir/ritonavir arms. The Solidarity Trial was established by WHO to find an effective COVID-19 treatment for hospitalized patients.

Status: The COVID-19 Treatment Guidelines Panel recommends against using lopinavir/ritonavir or other HIV protease inhibitors for the treatment of COVID-19, except in a clinical trial. The pharmacodynamics of lopinavir/ritonavir raise concerns about whether it is possible to achieve drug concentrations that can inhibit the SARS-CoV-2 proteases. In addition, lopinavir/ritonavir did not show efficacy in a moderately sized randomized controlled trial in patients with COVID-19.

References:

  • Publication: A Trial of Lopinavir–Ritonavir in Adults Hospitalized with Severe Covid-19. NEJM (05/07/20).
  • News Release: WHO discontinues hydroxychloroquine and lopinavir/ritonavir treatment arms for COVID-19. WHO (07/04/20).
  • NIH guidelines: Lopinavir/Ritonavir and Other HIV Protease Inhibitors. NIH (07/17/20).

Candidate: Ivermectin

Sponsors/Developers: Multiple developers.

Location: Multiple locations.

Clinical Trial IDs: NCT04422561, NCT04343092, NCT04425863 and several others.

Description: Ivermectin is a Food and Drug Administration (FDA)-approved antiparasitic drug that is used to treat several neglected tropical diseases, including onchocerciasis, helminthiases, and scabies. It is also being evaluated for its potential to reduce the rate of malaria transmission by killing mosquitoes that feed on treated humans and livestock. For these indications, ivermectin has been widely used and has demonstrated an excellent safety profile. Ivermectin acts by inhibiting the host importin alpha/beta-1 nuclear transport proteins, which are part of a key intracellular transport process that viruses hijack to enhance infection by suppressing the host antiviral response. Ivermectin is therefore a host-directed agent, which is likely the basis for its broad-spectrum activity in vitro against the viruses that cause dengue, Zika, HIV, and yellow fever.

In the ICON (Ivermectin in COvid Nineteen) study, a  retrospective cohort study of 280 consecutive hospitalized patients, Ivermectin was associated with lower mortality during treatment of COVID-19, especially in patients who required higher inspired oxygen or ventilatory support. These findings should be further evaluated with randomized controlled trials.

Add-on use of Ivermectin to hydroxychloroquine and azithromycin had better effectiveness, shorter hospital stay, and relatively safe compared with controls. however, a larger prospective study with longer follow up may be needed to validate these results.

An experimental treatment called IDEA based on four affordable drugs (ivermectin, dexamethasone, enoxaparin and aspirin ) already available on the market in Argentina showed promising results.

The COVID-19 Treatment Guidelines Panel recommends against the use of ivermectin for the treatment of COVID-19, except in a clinical trial.

Status: In a recent publication with 89 high-risk patients receiving ivermectin, the ivermectin treated patients became SARS-CoV-2 negative more quickly and fewer treated patients developed respiratory distress. Ivermectin-treated COVID-19 patients also had shorter hospital stays and was associated with a lower mortality rate in COVID-19 patients.

A french clinical-stage pharmaceutical firm MedinCell has commenced the first clinical trial of its Covid-19 prevention programme. The randomised, double-blind, exploratory phase I trial A has been designed to evaluate the pharmacokinetic profile, safety and tolerability of a continuous daily dosing regimen of Ivermectin in healthy volunteers.

References:

  • Publication: The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro. Antiviral Research (04/03/20).
  • NIH guidelines: NIH COVID-19 treatment guidelines. NIH (Last accessed 08/27/20).
  • Preprint: Effectiveness of Ivermectin as add-on Therapy in COVID-19 Management (Pilot Trial). medRxiv (07/08/20).
  • Preprint: ICON (Ivermectin in COvid Nineteen) study: Use of Ivermectin is Associated with Lower Mortality in Hospitalized Patients with COVID19. medRxiv (06/10/20).
  • Preprint: Safety and Efficacy of the combined use of ivermectin, dexamethasone, enoxaparin and aspirin against COVID-19. medRxiv (09/15/20).
  • Publication: Ivermectin treatment may improve the prognosis of patients with COVID-19. ScienceDirect (09/24/20).
  • Press Release: MedinCell initiates the first clinical trial of its Covid-19 prevention program(09/29/20).

Updated: 25 November, 2020.

  • Low-dose corticosteroid combined with immunoglobulin reverses deterioration in severe cases with COVID-19 [Link] (11/25/20)
  • Boehringer and Icahn School begin enrolment in COVID-19 trial [Link] (11/25/20)
  • NeuroRx and Relief announce initial successful results from expanded access use of rlf-100 (aviptadil) in patients with critical COVID-19 and severe comorbidity: 72% survival seen in ICU patients [Link] (11/25/20)
  • A Randomized Trial of Convalescent Plasma in COVID-19 Severe Pneumonia [Link] (11/25/20)
  • The effect of whey protein on viral infection and replication of SARS-CoV-2 and pangolin coronavirus in vitro [Link] (11/25/20)
  • Randomized double-blinded placebo-controlled trial of hydroxychloroquine with or without azithromycin for virologic cure of non-severe COVID-19 [Link] (11/25/20)
  • Targeted intracellular degradation of SARS-CoV-2 via computationally optimized peptide fusions  [Link] (11/25/20)
  • Cohort study to evaluate the effect of vitamin D, magnesium, and vitamin B12 in combination on progression to severe outcomes in older patients with coronavirus (COVID-19) [Link] (11/25/20)
  • Bellerophon Therapeutics Announces Results of Interim Analysis of Phase 3 COViNOX Study of INOpulse for the Treatment of COVID-19 [Link] (11/25/20)
  • CytoDyn Reaches Enrollment Target of 293 Patients for 2nd DSMC Interim Analysis of Phase 3 COVID-19 Trial and Expects to Enroll the Remaining 97 Patients in the Next Few Weeks to Complete the Trial This Year [Link] (11/25/20)
  • Prevention of severe COVID-19 in the elderly by early high-titer plasma  [Link] (11/25/20)
  • Septic shock and pneumonia triggered by SARS-CoV-2 could be treated by radiation-activated MSCs [Link] (11/25/20)
  • Anti-severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) potency of Mefloquine as an entry inhibitor in vitro [Link] (11/25/20)
  • Production of anti-SARS-CoV-2 hyperimmune globulin from convalescent plasma [Link] (11/25/20)
  • Camostat Mesylate May Reduce Severity of Coronavirus Disease [Link] (11/25/20)
  • Baricitinib Receives Emergency Use Authorization from the FDA for the Treatment of Hospitalized Patients with COVID-19 [Link] (11/20/20)
  • Researchers Create Nasal Spray for COVID-19 That May Already Be Safe for Humans [Link] (11/20/20)
  • BioLineRx Announces Initiation of Phase 1b Clinical Trial in Patients with Acute Respiratory Distress Syndrome (ARDS) Secondary to COVID-19 and Other Respiratory Viral Infections [Link] (11/20/20)
  • Effect of Vitamin D3 Supplementation vs Placebo on Hospital Length of Stay in Patients with Severe COVID-19: A Multicenter, Double-blind, Randomized Controlled Trial [Link] (11/20/20)
  • Anakinra in hospitalized patients with severe COVID-19 pneumonia requiring oxygen therapy: results of a prospective, open-label, interventional study [Link] (11/20/20)
  • A continuously self-sterilizing form of copper capable of 99% SARS-CoV-2 deactivation in 30 seconds [Link] (11/20/20)
  • RedHill Biopharma’s Second COVID-19 Candidate, RHB-107, Cleared by FDA for Phase 2/3 Study in Symptomatic COVID-19 Disease [Link] (11/20/20)
  • Tonix Pharmaceuticals Reports Positive Immune Response Results from COVID-19 Vaccine Candidate TNX-1800, Following Vaccination of Non-Human Primates [Link] (11/20/20)
  • Effects of inactivation method on SARS-CoV-2 virion proteins and structure [Link] (11/20/20)
  • Intravenous Immunoglobulin Plus Methylprednisolone Mitigate Respiratory Morbidity in Coronavirus Disease 2019 [Link] (11/20/20)
  • High-content screening of Thai medicinal plants reveals Boesenbergia rotunda extract and its component Panduratin A as anti-SARS-CoV-2 agents [Link] (11/18/20)
  • A natural food preservative peptide nisin can interact with the SARS-CoV-2 spike protein receptor human ACE2 [Link] (11/18/20)
  • An in-silico study on selected organosulfur compounds as potential drugs for SARS-CoV-2 infection via binding multiple drug targets [Link] (11/18/20)
  • Potential for personalised application of inhaled nitric oxide in COVID-19 pneumonia [Link] (11/18/20)
  • JAK inhibition reduces SARS-CoV-2 liver infectivity and modulates inflammatory responses to reduce morbidity and mortality  [Link] (11/18/20)
  • Fluvoxamine vs Placebo and Clinical Deterioration in Outpatients With Symptomatic COVID-19 [Link] (11/18/20)
  • Corticosteroids are associated with increased survival in elderly presenting severe SARS-Cov2 infection [Link] (11/18/20)
  • Reven reports positive data from Covid-19 drug trial [Link] (11/18/20)
  • AstraZeneca’s Calquence Fails Pair of Phase II COVID-19 Trials  [Link] (11/18/20)
  • Selva Therapeutics Announces First Dosing in Phase 1 Clinical Study of SLV213, a Potential Oral Treatment for COVID-19  [Link] (11/18/20)
  • Safety and efficacy of inhaled nebulised interferon beta-1a (SNG001) for treatment of SARS-CoV-2 infection: a randomised, double-blind, placebo-controlled, phase 2 trial [Link] (11/18/20)
  • Peginterferon-lambda for the treatment of COVID-19 in outpatients  [Link] (11/18/20)
  • Fluvoxamine vs Placebo and Clinical Deterioration in Outpatients With Symptomatic COVID-19: A Randomized Clinical Trial  [Link] (11/18/20)
  • Short term, high-dose vitamin D supplementation for COVID-19 disease: a randomised, placebo-controlled, study (SHADE study)  [Link] (11/18/20)
  • Mathematical analysis of Cordoba calcifediol trial suggests strong role for Vitamin D in reducing ICU admissions of hospitalized COVID-19 patients  [Link] (11/18/20)
  • Engineered trimeric ACE2 binds viral spike protein and locks it in “Three-up” conformation to potently inhibit SARS-CoV-2 infection [Link] (11/13/20)
  • Cold atmospheric plasma for SARS-CoV-2 inactivation [Link] (11/13/20)
  • Effect of Hydroxychloroquine on Clinical Status at 14 Days in Hospitalized Patients With COVID-19: A Randomized Clinical Trial [Link] (11/13/20)
  • Post Exposure Prophylaxis with Hydroxychloroquine (HCQ) for the Prevention of COVID-19, a Myth or a Reality? The PEP-CQ Study [Link] (11/13/20)
  • Baricitinib treatment resolves lower airway macrophage inflammation and neutrophil recruitment in SARS-CoV-2-infected rhesus macaques [Link] (11/13/20)
  • Nafamostat Mesylate in lipid carrier for nasal SARS-CoV2 titer reduction in a hamster model  [Link] (11/13/20)
  • Inhibition of SARS-CoV-2 in Vero cell cultures by peptide-conjugated morpholino oligomers  [Link] (11/13/20)
  • Molecular determinants of vascular transport of dexamethasone in COVID-19 therapy [Link] (11/13/20)
  • Cleveland Clinic Researchers Use “Big Data” Approach to Identify Melatonin as Possible COVID-19 Treatment [Link] (11/13/20)
  • In vitro: Natural Compounds (Thymol, Carvacrol, Hesperidine, And Thymoquinone) Against SARS-CoV2 Strain Isolated From Egyptian Patients  [Link] (11/13/20)
  • Early, low-dose, short-term methylprednisolone decreased the mortality in critical COVID-19 patients: a multicenter retrospective cohort study [Link] (11/13/20)
  • Novartis’ Ilaris Fails to Meet Endpoints in COVID-19 Study  [Link] (11/13/20)
  • Aspirin to be investigated as a possible treatment for COVID-19 in the RECOVERY trial [Link] (11/13/20)
  • Safety and efficacy of Artemisinin-Piperaquine for treatment of COVID-19: an open-label, non-randomized, and controlled trial [Link] (11/13/20)
  • RLF-100 (aviptadil) trial for respiratory failure to continue to full enrollment after review committee identified no safety concerns and no finding of futility [Link] (11/06/20)
  • Intranasal fusion inhibitory lipopeptide prevents direct contact SARS-CoV-2 transmission in ferrets [Link] (11/06/20)
  • Zinc-embedded fabrics can inactivate SARS-CoV-2 as well as influenza A virus [Link] (11/06/20)
  • Meta-analysis of 26 studies and 44,521 patients suggests hydroxychloroquine can lower mortality at low dose [Link] (11/06/20)
  • Tested plant juices and green tea show viricidal activity against both SARS-CoV-2 and influenza virus in vitro [Link] (11/06/20)
  • Treatment with zinc with ionophore is associated with reduced in-hospital mortality in a 3,473-patient multicenter study [Link] (11/04/20)
  • Brilacidin, a de novo designed synthetic small molecule, exerts potent inhibition of SARS-CoV-2 in human lung cell line and a monkey cell line [Link] (11/04/20)
  • Open-label prospective trial of 130 patients (NCT04357366) shows suPAR biomarker-guided anakinra treatment is associated with decrease of the risk for severe respiratory failure [Link] (11/04/20)
  • 5-amino levulinic acid, a naturally synthesized amino acid, potently inhibited SARS-CoV-2 infection in vitro [Link] (11/04/20)

Select strategies are detailed in the section below:

Candidate: OLUMIANT (Baricitinib, LY3009104).

Developers: Eli Lilly, Incyte, National Institute of Allergy and Infectious Diseases (NIAID), Emory University.

Clinical Trial Ids: COV/BARRIER/NCT04421027 (Phase 3), ACTT-2/NCT04401579 (Phase 3)

Locations: USA, UK, Argentina, Brazil and others.

Description: Many patients with severe respiratory disease due to COVID-19 have features consistent with cytokine release syndrome. Due to increased activation of the JAK/STAT pathway, it is postulated that JAK-inhibitors might have a useful role in treating these patients.

OLUMIANT is a once-daily, oral JAK inhibitor approved in the U.S. for the treatment of adults with moderately to severely active rheumatoid arthritis who have had an inadequate response to one or more TNF inhibitor therapies, and approved outside of the U.S. for patients with moderately to severely active rheumatoid arthritis who have had an inadequate response to one or more DMARDs. There are four known JAK enzymes: JAK1, JAK2, JAK3 and TYK2. JAK-dependent cytokines have been implicated in the pathogenesis of a number of inflammatory and autoimmune diseases. OLUMIANT has greater inhibitory potency at JAK1, JAK2 and TYK2 relative to JAK3; however, the relevance of inhibition of specific JAK enzymes to therapeutic effectiveness is not currently known.

Lilly and Incyte announced on September 14, initial data emerging from the Adaptive COVID-19 Treatment Trial (ACTT-2) sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH). ACTT-2 included more than 1,000 patients and began on May 8 to assess the efficacy and safety of a 4-mg dose of baricitinib plus remdesivir versus remdesivir in hospitalized patients with COVID-19. Baricitinib in combination with remdesivir met the primary endpoint of reduction of time to recovery in comparison with remdesivir. Study investigators noted an approximately one-day reduction in median recovery time for the overall patient population treated with baricitinib in combination with remdesivir versus those treated with remdesivir. This finding was statistically significant. The study also met a key secondary endpoint comparing patient outcomes at Day 15 using an ordinal 8-point scale ranging from fully recovered to death.

Lilly will review the ACTT-2 data with NIAID and assess any impact on COV-BARRIER, the Phase 3 randomized, double-blind, placebo-controlled study it initiated in June to evaluate the efficacy and safety of baricitinib versus background therapy in hospitalized adults with COVID-19.

A preprint from Emory University showed investigation of the immunologic and virologic efficacy of baricitinib in a rhesus macaque model of SARS-CoV-2 infection. Animals treated with baricitinib showed reduced immune activation, decreased infiltration of neutrophils into the lung, reduced NETosis activity, and more limited lung pathology. Moreover, baricitinib treated animals had a rapid and remarkably potent suppression of alveolar macrophage derived production of cytokines and chemokines responsible for inflammation and neutrophil recruitment. Viral shedding measured from nasal and throat swabs, bronchoalveolar lavages and tissues was not reduced with baricitinib.

Additional data was shared by Lilly on October 08 showing baricitinib in combination with remdesivir reduced time to recovery and improved clinical outcomes for patients with COVID-19 infection compared with remdesivir. This finding was part of additional efficacy and safety data from the Adaptive COVID-19 Treatment Trial (ACTT-2). As previously reported, ACTT-2 achieved the primary endpoint, demonstrating that the overall patient population treated with baricitinib in combination with remdesivir improved their median time to recovery from 8 to 7 days in comparison to remdesivir, a 12.5% improvement (incidence rate ratio: 1.16; 95% CI: 1.01, 1.32; p=0.04).

Status: On 19 November 2020, Eli Lilly announced that the U.S. FDA issued an Emergency Use Authorization (EUA) for the distribution and emergency use of baricitinib to be used in combination with remdesivir in hospitalized adult and pediatric patients two years of age or older with suspected or laboratory confirmed COVID-19 who require supplemental oxygen, invasive mechanical ventilation, or extracorporeal membrane oxygenation (ECMO).

The EUA is based on data from the Adaptive COVID-19 Treatment Trial (ACTT-2), a randomized double-blind, placebo-controlled study to evaluate the efficacy and safety of baricitinib in combination with remdesivir versus placebo with remdesivir in hospitalized patients with or without oxygen requirements conducted by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH). All patients received standard supportive care by the trial site hospital. The recommended dose for this EUA is baricitinib 4-mg once daily for 14 days or until hospital discharge.

References:

  • Press Release: Baricitinib in Combination with Remdesivir Reduces Time to Recovery in Hospitalized Patients with COVID-19 in NIAID-Sponsored ACTT-2 Trial. Eli Lilly (09/14/20).
  • Press Release: Lilly Begins a Phase 3 Clinical Trial with Baricitinib for Hospitalized COVID-19 Patients. Eli Lilly (06/15/20).
  • Preprint: Baricitinib treatment resolves lower airway inflammation and neutrophil recruitment in SARS-CoV-2-infected rhesus macaques. bioRxiv (09/16/20).
  • Press Release: Baricitinib has Significant Effect on Recovery Time, Most Impactful in COVID-19 Patients Requiring Oxygen. Eli Lilly (10/08/20).
  • Press Release: Baricitinib Receives Emergency Use Authorization from the FDA for the Treatment of Hospitalized Patients with COVID-19. Eli Lilly (11/19/20).

Candidate: Low-dose Dexamethasone.

Clinical Trial IDs: ISRCTN50189673 (Phase II/III), EudraCT 2020-001113-21 (Phase II/III), NCT04381936 (Phase II/III).

Locations: United Kingdom.

Developers: Randomised Evaluation of COVid-19 thERapY (RECOVERY) Trial- This trial is supported by a grant to the University of Oxford from UK Research and Innovation/National Institute for Health Research (NIHR) and by core funding provided by NIHR Oxford Biomedical Research Centre, Wellcome,  the Bill and Melinda Gates Foundation, the Department for International Development, Health Data Research UK, the Medical Research Council Population Health Research Unit, and NIHR Clinical Trials Unit Support Funding.

Description: In March 2020, the RECOVERY trial was established as a randomised clinical trial to test a range of potential treatments for COVID-19, including low-dose dexamethasone (a steroid treatment). Over 11,500 patients have been enrolled from over 175 NHS hospitals in the UK. On 8 June, recruitment to the dexamethasone arm was halted since, in the view of the trial Steering Committee, sufficient patients had been enrolled to establish whether or not the drug had a meaningful benefit. A total of 2104 patients were randomized to receive dexamethasone 6 mg once per day (either by mouth or by intravenous injection) for ten days and were compared with 4321 patients randomized to usual care alone. Among the patients who received usual care alone, 28-day mortality was highest in those who required ventilation (41%), intermediate in those patients who required oxygen only (25%), and lowest among those who did not require any respiratory intervention (13%). Dexamethasone reduced deaths by one-third in ventilated patients (rate ratio 0.65 [95% confidence interval 0.48 to 0.88]; p=0.0003) and by one fifth in other patients receiving oxygen only (0.80 [0.67 to 0.96]; p=0.0021). There was no benefit among those patients who did not require respiratory support (1.22 [0.86 to 1.75]; p=0.14).

Status: In a prospective meta-analysis of 7 randomized trials that included 1703 patients of whom 647 died (including the RECOVERY trial), 28-day all-cause mortality was lower among patients who received corticosteroids compared with those who received usual care or placebo (summary odds ratio, 0.66).

On the basis of the preliminary report from the RECOVERY trial, the COVID-19 Treatment Guidelines Panel recommends using dexamethasone 6 mg per day for up to 10 days or until hospital discharge, whichever comes first, for the treatment of COVID-19 in hospitalized patients who are mechanically ventilated and in hospitalized patients who require supplemental oxygen but who are not mechanically ventilated. If dexamethasone is not available, the Panel recommends using alternative glucocorticoids such as prednisonemethylprednisolone, or hydrocortisone.

References:

  • News: Low-cost dexamethasone reduces death by up to one third in hospitalised patients with severe respiratory complications of COVID-19. Recovery Trial (06/16/20).
  • Preprint: Effect of Dexamethasone in Hospitalized Patients with COVID-19: Preliminary Report. medRxiv (06/22/20).
  • Publication: Dexamethasone in Hospitalized Patients with Covid-19 – Preliminary Report. NEJM (07/17/20).
  • Meta-analysis: Association Between Administration of Systemic Corticosteroids and Mortality Among Critically Ill Patients With COVID-19. JAMA (09/02/20).
  • RECOVERY Trial: Website for Randomised Evaluation of COVid-19 thERapY (RECOVERY) Trial, as accessed on 09/21/20.
  • NIH: Guidelines and recommendations for Dexamethasone, as accessed on 09/21/20.

FDA has issued guidance to provide recommendations to health care providers and investigators on the administration and study of investigational convalescent plasma collected from individuals who have recovered from COVID-19 (COVID-19 convalescent plasma) during the public health emergency.

Convalescent plasma that contains antibodies to SARS-CoV-2 is being studied for administration to patients with COVID-19. Use of convalescent plasma has been studied in outbreaks of other respiratory infections, including the 2003 SARS-CoV-1 epidemic, the 2009-2010 H1N1 influenza virus pandemic, and the 2012 MERS-CoV epidemic.

Although promising, convalescent plasma has not yet been shown to be safe and effective as a treatment for COVID-19. Therefore, it is important to study the safety and efficacy of COVID-19 convalescent plasma in clinical trials.

On August 23, 2020, the FDA issued an Emergency Use Authorization (EUA) for COVID-19 convalescent plasma for the treatment of hospitalized patients. The COVID-19 Treatment Guidelines Panel (the Panel) reviewed the available evidence from published and unpublished data on convalescent plasma for the treatment for COVID-19, including the FDA analyses that supported the EUA.

The FDA analysis of data on a subset of hospitalized patients from the Mayo Clinic’s Expanded Access Program (EAP) compared outcomes in patients who received convalescent plasma with high titers of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neutralizing antibodies to outcomes in patients who received plasma with low titers and found no difference in 7-day survival overall. Among patients who were not intubated, 11% of those who received convalescent plasma with high antibody titers died within 7 days of transfusion compared with 14% of those who received convalescent plasma with low antibody titers. Among those who were intubated, there was no difference in 7-day survival. Although these data suggest that convalescent plasma with high antibody titers may be beneficial in nonintubated patients, uncertainty remains about the efficacy and safety of convalescent plasma due to the lack of a randomized control group and possible confounding in the Mayo Clinic’s EAP. Additionally, antibody levels in currently available COVID-19 convalescent plasma are highly variable, and assays to determine the effective antibody titers remain limited.

Based on the available evidence, the Panel has determined the following:

  • There are insufficient data to recommend either for or against the use of convalescent plasma for the treatment of COVID-19.
  • Available data suggest that serious adverse reactions following the administration of COVID-19 convalescent plasma are infrequent and consistent with the risks associated with plasma infusions for other indications. The long-term risks of treatment with COVID-19 convalescent plasma and whether its use attenuates the immune response to SARS-CoV-2, making patients more susceptible to reinfection, have not been evaluated.
  • Convalescent plasma should not be considered standard of care for the treatment of patients with COVID-19.
  • Prospective, well-controlled, adequately powered randomized trials are needed to determine whether convalescent plasma is effective and safe for the treatment of COVID-19. Members of the public and health care providers are encouraged to participate in these prospective clinical trials.

References:

  • CONCOVID Preprint: Convalescent Plasma for COVID-19. A randomized clinical trial (NCT04342182). medRxiv (07/03/20).
  • Publication: Effect of Convalescent Plasma Therapy on Time to Clinical Improvement in Patients With Severe and Life-threatening COVID-19: A Randomized Clinical Trial (ChiCTR2000029757). JAMA (06/03/20).
  • Mayo Clinic Preprint: Early Safety Indicators of COVID-19 Convalescent Plasma in 5,000 Patients. medRxiv 05/14/20).
  • News: FDA Issues Emergency Use Authorization for Convalescent Plasma as Potential Promising COVID–19 Treatment. FDA (08/23/20).
  • FDA guidance: Recommendations for Investigational COVID-19 Convalescent Plasma (09/01/20).
  • Mayo Clinic: Safety Update – COVID-19 Convalescent Plasma in 20,000 Hospitalized Patients (09/01/20).

Updated: 25 November, 2020.

The table lists various ongoing treatment efforts (Antibodies, Antivirals, Cell-based therapies and others) from developers and sponsors globally to identify a safe and efficacious solution to the pandemic. Data is collated from various sources including WHO and Milken Institute trackers.

Updated: November 10, 2020.

COVID-19 Clinical Trials: An Overview

Researchers and clinicians all over the world have reacted to the COVID-19 pandemic and the ensuing public health crisis with a colossal worldwide effort to discover a treatment. With increasing number of global cases and fatalities, the world waits for positive results from these ongoing trials. Several existing antivirals, traditional and alternative medicines, investigative or repurposed compounds, support devices as well as procedures, supplements are being explored in the context of SARS-CoV-2 infection.

The pandemic has changed the way trials are being conducted, with several radical changes in terms of recruitment, obtaining consent remotely, telemedical monitoring and implementation of more innovative trial designs. There is a need to make these positive changes instigated by the pandemic sustainable [1].

The World Health Organization’s International Clinical Trials Registry Platform (WHO ICTRP) ensures that “a complete view of research is accessible to all those involved in health care decision making”. Information in the WHO ICTRP comprises of structured data from several major clinical trial databases from countries or regions of the world, including but not limited to the ClinicalTrials.gov [2], Chinese Clinical Trial Registry (ChiCTR) [3], The Clinical Trials Registry- India (CTRI) [4], Iranian Registry of Clinical Trials [5], European Union Clinical Trials Register [6] and the ISRCTN register [7].

As of November 10, 2020, there are 6533 trials registered in the WHO ICRTRP database for COVID-19, with 3850 Interventional trials and rest comprising majorly of Observational studies (2594), Diagnosis tests (48), and others [8].

Of note, is the SOLIDARITY trial [9]. Solidarity is an international clinical trial to help find an effective treatment for COVID-19, launched by the WHO and partners. The Solidarity Trial tests various options against standard of care to assess their  effectiveness against COVID-19. Based on evidence from laboratory, animal and clinical studies, the following treatment options were selected – Remdesivir, Lopinavir/Ritonavir, Lopinavir/Ritonavir with Interferon beta-1a, Chloroquine or Hydroxychloroquine. Other drugs can be added based on emerging evidence. By October, the Phase II/III SOLIDARITY trial for COVID-19 was the world’s largest randomized clinical trial for the treatment of COVID-19, with 11,266 patients enrolled from 405 hospitals located in more than 30 countries. The Solidarity Trial published interim results on 15 October 2020. It found that all 4 treatments evaluated (remdesivir, hydroxychloroquine, lopinavir/ritonavir and interferon) had little or no effect on overall mortality, initiation of ventilation and duration of hospital stay in hospitalized patients. So far, only corticosteroids have been proven effective against severe and critical COVID-19. Previously, on 4 July 2020, WHO had accepted the recommendation from the Solidarity Trial’s International Steering Committee to discontinue the trial’s hydroxychloroquine and lopinavir/ritonavir arms.

The US FDA has created a special emergency program for possible coronavirus therapies, the Coronavirus Treatment Acceleration Program (CTAP). As per the program guidelines, it aims to use every available method to move new treatments to patients as quickly as possible, while at the same time finding out whether they are helpful or harmful [10]. The CTAP Dashboard provides users with a snapshot of development of potential COVID-19 therapeutics. As of October 31, 2020, the CTAP dashboard lists 560+ available therapies with 370+ clinical trials reviewed, with 5 of the available therapies approved for Emergency Use. Only one among the therapies have been FDA approved so far (Figure 1).

Figure 1: Treatments reviewed by CTAP – Numbers correspond to number of safe to proceed INDs. Excludes INDs related to vaccines (Source: CTAP dashboard [10]). There were 90+ early stage trials and 270+ late stage (Phase 2-4) trials from U. S. included in the analysis.

As per FDA classification, the categories in this bar chart span several categories –

  • Antiviral drugs keep viruses from multiplying and are used to treat many viral infections (such as HIV, Herpes, Hepatitis C, and influenza). 
  • Immunomodulators are aimed at tamping down the body’s own immune reaction to the virus, in cases where the body’s reaction basically goes overboard and starts attacking the patient’s own organs.
  • Neutralizing antibody therapies may help individuals fight the virus and include manufactured antibodies, animal-sourced antibody therapies, and blood-derived products such as convalescent plasma and hyperimmune globulin, which contain antibodies taken from people who have previously had COVID-19.
  • Cell therapy products include cellular immunotherapies and other types of both autologous and allogeneic cells, such as stem cells, and related products.
  • Gene therapy products seek to modify or manipulate the expression of a gene or to alter the biological properties of living cells for therapeutic use.

The Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) partnership [11] was announced on April 17, 2020 by  National Institutes of Health (NIH), with coordination by the Foundation for the National Institutes of Health (FNIH) involving a collaboration among government and industry partners, including FDA, to prioritize vaccine and therapeutic candidates, streamline clinical trials, and rapidly expand the clinical research resources focused on developing therapies [12]. ACTIV continues to grow and now involves several academic and industry partners (20 biopharmaceutical companies), and up to 8 different government agencies. ACTIV also works closely with other COVID-19 efforts, including FDA and BARDA’s Medical Countermeasures Task Force, the Bill & Melinda Gates Foundation, the Wellcome Trust, the European Commission, the UK government, and the World Health Organization.

Several tracker projects [13, 14] classify trials based on strategies tested against COVID-19. Analysis of major categories highlights the top treatments being investigated world-wide as shown in Figure 2.

Figure 2: A comparison of treatments as a measure of trials they are part of, as on 11 November 2020. Data was obtained from WHO ICTRP [8] and Trials Tracker Projects [13, 14].

Ever since the first clinical trial was registered early this year, trial registrations have seen an unprecedented pace. The number of registrations on a daily basis since early January 2020 is shown in Figure 3.

Figure 3: The pandemic pace of clinical trial registrations on leading platforms, as per data obtained from WHO ICTRP [8] on 10 November 2020.

For a routinely updated list of all clinical trials with details and links to the registry page, please visit the adjacent tab “List of Clinical Trials”.

Last Updated: November 14, 2020.

References:

  1. Gaba, P., Bhatt, D.L. The COVID-19 pandemic: a catalyst to improve clinical trials. Nat Rev Cardiol (2020). https://doi.org/10.1038/s41569-020-00439-7
  2. ClinicalTrials.gov Registry. https://clinicaltrials.gov/
  3. Chinese Clinical Trial Registry (ChiCTR). http://www.chictr.org.cn/abouten.aspx
  4. The Clinical Trials Registry- India (CTRI). http://ctri.nic.in/Clinicaltrials/login.php
  5. Iranian Registry of Clinical Trials. https://www.irct.ir/
  6. European Union Clinical Trials Register. https://www.clinicaltrialsregister.eu/ctr-search/search
  7. ISRCTN register. https://www.isrctn.com/
  8. World Health Organization’s International Clinical Trials Registry Platform (WHO ICTRP). https://www.who.int/ictrp/en/
  9. “Solidarity” clinical trial for COVID-19 treatments. https://www.who.int/emergencies/diseases/novel-coronavirus-2019/global-research-on-novel-coronavirus-2019-ncov/solidarity-clinical-trial-for-covid-19-treatments
  10. Coronavirus Treatment Acceleration Program (CTAP) | FDA. https://www.fda.gov/drugs/coronavirus-covid-19-drugs/coronavirus-treatment-acceleration-program-ctap
  11. ACCELERATING COVID-19 THERAPEUTIC INTERVENTIONS AND VACCINES (ACTIV). https://www.nih.gov/research-training/medical-research-initiatives/activ
  12. NIH to launch public-private partnership to speed COVID-19 vaccine and treatment options. https://www.nih.gov/news-events/news-releases/nih-launch-public-private-partnership-speed-covid-19-vaccine-treatment-options
  13. The TrialsTracker project dashboard. http://covid19.trialstracker.net/
  14. Global Coronavirus COVID-19 Clinical Trial Tracker. https://covidtrialstracker.org/

COVID-19 Global Funding Response

The world is facing an unprecedented challenge with communities and economies everywhere affected by the growing COVID-19 pandemic. IMF estimates suggest that, for each month the pandemic persists, $500 billion is lost from the global economy. The world is coming together to combat the COVID-19 pandemic bringing together governments, organizations and individuals from across industries and sectors to help respond to this global outbreak. The outpour of global solidarity and support sparked by this shared challenge has been phenomenal.

An analysis of data available on the Devex funding database reveals over $20.4 trillion committed to the COVID-19 response to date. Since the beginning of 2020, governments, bilateral and multilateral donors, development banks, philanthropic organizations, and the private sector have all played a role in contributing money, equipment, expertise, and more. As of November 22, 2020, investments totaling $186.6 billion have been made through 896 program announcements and 781 grants have supported $2.8 billion worth of investment. As for business opportunities, 2,003 tenders have seen $4.7 billion invested through program delivery and service partners, while 1,073 contracts have delivered $1.6 billion on the ground.

The WHO Strategic Preparedness and Response Plan outlines a funding need of at least US$675 million for critical response efforts in countries most in need of help through April 2020. People and organizations who want to help fight the pandemic and support WHO and partners can now donate through the COVID-Solidarity Response Fund for WHO at www.COVID19ResponseFund.org. Up to US$238 million has already been raised as of 23 October, 2020 from more than 651,000 individuals, companies and philanthropies.

Figure: An overview of how the COVID-19 Solidarity Response Fund is being utlized in response to the pandemic.

The Coalition for Epidemic Preparedness Innovations (CEPI) is a global alliance financing and coordinating the development of vaccines against emerging infectious diseases. CEPI has received support from founding member Norway (US$210 million), UK government (US$270 million), Government of Belgium (US$5.5 million), Government of Canada (US$28.2 million), Greece (US$1.6 million) and German Government’s Federal Ministry (US$157 million).

CEPI, alongside Gavi and the World Health Organisation, launched COVAX – the vaccines pillar of the ACT Accelerator – with the aim of ending the acute phase of the pandemic by the end of 2021. COVAX is the solution that will deliver fair, equitable access to vaccines for every country that participates. Together the aim is to produce 2 billion doses of vaccine and distribute them globally and fairly in 2021. To support the vaccine R&D that is critical to achieving this goal, CEPI estimates that it needs $2.1bn to progress three vaccines to licensure, which will be made available to the world through COVAX. Through COVAX, the risks and benefits of developing and producing vaccines are shared across countries. COVAX works by pooling financial resources to develop vaccines, purchase them at scale, and investing up-front in manufacturing so that vaccines are ready to be distributed as soon as they are licensed. Countries participating in COVAX can access CEPI’s portfolio of COVID-19 vaccine candidates – the largest in the world – which is managed by CEPI’s R&D experts.

To date, CEPI has secured financial support from the Bill & Melinda Gates Foundation,  Wellcome Trust, the European Commission, and the governments of Australia, Belgium, Canada, Denmark, Ethiopia, Germany, Japan, Mexico, Norway and the United Kingdom. In response to call the Governments of Austria, Australia, Belgium, Canada, European Commission, Finland, France, Greece, Germany, Iceland, Italy, Japan, Luxembourg, Kingdom of Saudi Arabia, Norway, the Netherlands, New Zealand, Serbia, Spain, Switzerland, and the United Kingdom, alongside private sector companies and donations through the UN Foundation COVID-19 Solidarity Response Fund, have pledged $1.4 billion in financial contributions.

Through the Bill and Melinda Gates Foundation, the Microsoft founder and philanthropist plan to help fund factories for promising vaccines, even before seeing conclusive data. The foundation has committed more than $350 million to support the global response to COVID-19. This includes $100 million to Gavi’s new COVID-19 Vaccine Advance Market Commitment, to support its future efforts to deliver COVID-19 vaccines to lower-income countries. In addition to the more than $350 million committed, the foundation will also leverage a portion of its Strategic Investment Fund, which addresses market failures and helps make it attractive for private enterprise to develop affordable and accessible health products. For example, the foundation is collaborating with Gavi and the Serum Institute of India to accelerate the manufacture and delivery of up to 100 million doses of COVID-19 vaccines for low- and middle-income countries. $150 million came from the Strategic Investment Fund. The Gates Foundation, along with Wellcome and Mastercard, are the founding funders of the COVID-19 Therapeutics Accelerator. The Accelerator is intended to play a catalytic role by accelerating and evaluating new and repurposed drugs to respond to COVID-19 in the immediate term, and other viruses in the longer-term – up to $50 million of the commitment will go towards supporting the COVID-19 Therapeutics Accelerator.

Biomedical Advanced Research and Development Authority (BARDA) part of the HHS Office of the Assistant Secretary for Preparedness and Response, was established to aid in securing our nation from chemical, biological, radiological, and nuclear (CBRN) threats, as well as from pandemic influenza (PI) and emerging infectious diseases (EID). BARDA supports the transition of medical countermeasures such as vaccines, drugs, and diagnostics from research through advanced development towards consideration for approval by the FDA and inclusion into the Strategic National Stockpile. BARDA has updated its Broad Agency Announcements (BAAs) to focus exclusively on addressing the COVID-19 threat. BARDA’s annual budget of $512 Million has been supplemented by an additional $3.5 billion through the recently passed Coronavirus Aid, Relief, and Economic Security (CARES) Act. The additional funding is allocated for necessary expenses of manufacturing, production, and purchase of various supplies and services. AstraZeneca recently received $1B in BARDA funding to advance vaccine. Another leading candidate, Moderna received $483 million BARDA award for vaccine development, while it awarded $450 million to Janssen Pharmaceuticals, a division of Johnson & Johnson, to develop a vaccine.

On 4 May 2020, the EU and its partners hosted an international pledging conference which has now raised €9.8 billion in pledges from donors worldwide to kick-start the global cooperation. This includes a pledge of €1.4 billion from the Commission of which €1 billion comes from Horizon 2020. The EU plays a central role is supporting and coordinating research on infectious diseases, with €4.1 billion invested from 2007 to 2019 through the 7th Framework Programme and Horizon 2020, which foresees further commitments in 2020 in addition to the €1 billion pledge for coronavirus research. This has included initiatives to coordinate European efforts to address antimicrobial resistance, as well as preparedness and emergency response to outbreaks (Ebola, Zika). From the Horizon 2020, €620 million has already been mobilised, and a further €394 million has been pledged.

The Board of Directors of the European Investment Bank (EIB) has agreed on the structure and business approach of the Pan-European Guarantee Fund (EGF) to tackle the economic consequences of the COVID-19 pandemic. The Fund was endorsed by the European Council as part of the overall EU COVID-19 response package. It will enable the EIB Group to scale up its support for mostly small and medium-sized European companies, providing up to €200 billion of additional financing.

The Global Fund, the largest multilateral funder of health systems worldwide, is providing immediate funding of up to US$1 billion to help countries fight COVID-19, mitigate the impacts on lifesaving HIV, TB and malaria programs, and prevent fragile health systems from being overwhelmed. Under the World Health Organization’s leadership, the Global Fund is using its experience working with partners and governments in more than 100 countries to coordinate our response on a massive global scale.

Multiple National Institutes of Health (NIH) Institutes have issued a Notice of Special Interest (NOSI) to provide funding for research topics related to COVID-19. National Institute on Aging (NIA), National Institute of Mental Health (NIMH), The National Heart, Lung, Blood Institute (NHLBI), National Institute of Allergy and Infectious Diseases (NIAID), National Institute of General Medical Sciences (NIGMS), National Center for Advancing Translational Sciences (NCATS), National Institute of Environmental Health Sciences (NIEHS), and National Institute of Drug Abuse (NIDA) are providing opportunities under the NIH.

Updated: November 25, 2020.

The following table lists funding opportunities listed on various public platforms including the NIH grants, JHU, Frontiers, and Brown University COVID-19 funding databases.

Updated: 25 November, 2020.

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