COVID-19 Monoclonal Antibodies

COVID-19 Monoclonal Antibodies 2023

According to the U.S. National Institutes of Health (N.I.H.), monoclonal antibody (mAb) products that target the SARS-CoV-2 coronavirus spike protein produce clinical benefits in treating COVID-19. According to the NIH, mAb treatments block SARS-CoV-2 from entering cells in the human body. The U.S. Department of Health and Human Services (H.H.S.) $5 billion Project NextGen, Defeating SARS-CoV-2 and Preparing for the Next Pandemic, includes mAbs that can weather viral evolution against new threats from beta-coronaviruses. On August 22, 2023, the Biomedical Advanced Research and Development Authority (BARDA) announced it would fund up to 70% of Regeneron Inc.'s costs for certain clinical development activities for a next-generation mAb therapy with broad neutralizing activity against SARS-CoV-2. The new contract has an estimated value of up to approximately $326 million of government funding.

As of January 26, 2023, the U.S. Food and Drug Administration (FDA) had withdrawn its authorization(s) for mAbs. However, on April 4, 2023, InflaRx N.V.'s Gohibic (vilobelimab), a first-in-class monoclonal anti-human complement factor C5a antibody, was granted an Emergency Use Authorization (E.U.A.) by the U.S. Food and Drug Administration (F.D.A.) for the treatment of COVID-19 in hospitalized adults when initiated within 48 hours of receiving invasive mechanical ventilation, or extracorporeal membrane oxygenation.

The U.K. Medicines and Healthcare Products Regulatory Agency (MHRA), European Medicines Agency (E.M.A.), Canada, China, and Japan continue reviewing specific mAbs. For example, the E.M.A. published Efficacy of mAbs in the context of rapidly evolving SARS-CoV-2 variants on January 15, 2023. Additionally, the World Health Organization (WHO) Lists various mAbs therapies as of April 2023. The Annals of Internal Medicine published results from a study on April 4, 2023, that concluded early mAb treatment among outpatients with COVID-19 is associated with a lower risk for hospitalization or death.

COVID-19 antivirals and vaccines are available as of July 2023.

Monoclonal Antibodies For Immunocompromised 2023

About seven million immunocompromised Americans, Including Organ Transplant Recipients and Cancer Patients, are vulnerable to the worst effects of COVID-19 because some vaccines don't trigger sufficient protective immune responses, says the U.S. Centers for Disease Control and Prevention (C.D.C.). On April 14, 2023, AstraZeneca presented data regarding the implementation of Evusheld (AZD7442) (tixagevimab/cilgavimab) COVID-19 pre-exposure prophylaxis in the largest H.M.O. in Israel: real-world uptake and sociodemographic and clinical characteristics across immunocompromised patient groups.

COVID-19 mAbs Globally Authorized.

Brii Biosciences Limited's amubarvimab / romlusevimab combination (BRII-196/BRII-198) is approved in China but not in the U.S.A. On April 18, 2023, a study funded by the U.S. government found administering amubarvimab plus romlusevimab was safe and significantly reduced the risk for hospitalization and/or death among nonhospitalized adults with mild to moderate SARS-CoV-2 infection at high risk for progression to severe disease.

Celltrion Healthcare Remsima®, the world's first mAbs biosimilar, received marketing authorization in 110 countries for treating Rheumatoid Arthritis. In the U.S., this FDA-approved product's name is InflectrIn. In addition, a. Celltrion's Regdanvimab (Regkirona) is authorized in Korea, Europe, Indonesia, Brazil, Peru, and Australia.

COVID-19 Monoclonal Antibody 'Paused'

Regeneron's REGEN-COV (casirivimab-imdevimab) is a potent, virus-neutralizing antibody that binds non-competitively to the critical receptor binding domain of the virus's spike protein. The E.M.A. continues authorization of casirivimab-imdevimab. First granted Emergency Use Authorization in November 2020, the antibody cocktail was used as a COVID-19 treatment and preventative for millions of people around the globe, with nearly 3 million doses delivered to the U.S. Government between 2020 and 2022.

AstraZeneca (AZN) COVID-19 Antibody combination Evusheld (tixagevimab and cilgavimab) was authorized to help reduce the incidence of symptomatic COVID-19. However, as of January 26, 2023, Evusheld's F.D.A. authorization was withdrawn. As of April 27, 2023, AZN reported $127 million in revenue from COVID-19 mAbs (Q1 2022: $469m).

Eli Lilly's Bebtelovimab is a neutralizing SARS-CoV-2 spike glycoprotein receptor-binding domain-specific antibody. On February. 11, 2022, the U.S. F.D.A. issued an Authorization. Then, on November 30, 2022, the F.D.A. withdrew its authorization.

Vir Biotechnology, Inc. and G.S.K.'s Sotrovimab (Xevudy) is a fully human anti-SARS-CoV-2 monoclonal antibody selected based on its potential to neutralize the virus in vitro, kill infected cells, provide a high barrier to resistance, and achieve high concentrations in the lungs. The European Commission (E.C.) authorized Sotrovimab on December 17, 2021. The WHO suggests treatment with sotrovimab, conditional to those at the highest risk of hospitalization. The E.M.A. continues authorization Xevudy. 

Eli Lilly's (NYSE: L.L.Y.) Bamlanivimab and etesevimab neutralizing IgG1 monoclonal antibody (mAb) combination is directed against the spike protein SARS-CoV-2 coronavirus. Bamlanivimab's Revised Fact Sheet was published on December 20, 2021. On January 27, 2022, the F.D.A. did not authorize this mAbs. 

Olumiant (baricitinib) Eli Lilly Nederland B.V., Marketing authorization evaluation by the E.M.A. started on 23/11/2021 and was withdrawn from marketing authorization evaluation on 07/12/2022.

COVID-19 Monoclonal Antibodies Experimental 2023

Sinovac Biotech Ltd. completed the phase I clinical trial for its broad-spectrum neutralizing antibody product, the Anti-COVID-19 Antibody SA55 Injection, and has entered the phase II clinical trial. Their studies underscore the SA55's efficacy in neutralizing the omicron variant and its sublineages, including BA.5, BF.7, BQ.1.1, XBB.1.5, BA.2.86 and the currently dominant strain, EG.5. Xie noted that SA55 is reportedly the only clinical antibody that SARS-CoV-2 hasn't escaped.

Adagio Therapeutic's Adintrevimab (ADG20) is a potent, broadly neutralizing antibody for preventing and treating COVID-19. A study published on June 13, 2023, found the relative risk reduction (R.R.R.) for participants who received an injection as post-exposure prophylaxis was 74.9%. As part of pre-exposure prophylaxis, the R.R.R. was 71.1%.

AstraZeneca's SARS-CoV-2 mAbs AZD3152 potently neutralizes historical and currently circulating variants. Trial in progress: a Phase I/III, randomized, modified double-blind, placebo- and active-controlled pre-exposure prophylaxis study of the SARS-CoV-2–neutralizing antibody AZD3152 (SUPERNOVA).

Invivyd, Inc.'s VYD222 is one of the mAb components of NVD200, a combination product. VYD222 was engineered from adintrevimab, Invivyd's investigational mAb with a robust safety data package, and demonstrated clinically meaningful results in global Phase 3 clinical trials for preventing and treating COVID-19. VYD222 has advanced into the clinic as a novel monoclonal antibody therapeutic option for COVID-19. The U.S. F.D.A. cleared its Investigational New Drug application for VYD222 on April 25, 2023. On June 22, 2023, Invivyd announced positive Initial Data from the ongoing Phase 1 clinical trial. On June 26, 2023, the company announced it had reached general alignment with the U.S. F.D.A. on a pathway to potential E.U.A. for VYD222. On July 17, 2023, the company announced additional positive initial data from its ongoing Phase 1 healthy volunteer clinical trial of VYD222, Serum samples from all dose levels tested showed robust neutralization activity against Omicron XBB.1.5, one of the dominant SARS-CoV-2 variants circulating globally.

Tonix Pharmaceuticals - TNX-3600 are fully human mAbs generated from SARS-CoV-2+ asymptomatic individuals or COVID-19 convalescent patients. And TNX-4100 are murine mAbs and their humanized counterparts generated from mice immunized with SARS-CoV-2 spike protein. Since mice have a different repertoire of antibodies than humans, murine mAbs have the potential for neutralizing a broader spectrum of SARS-CoV-2 variants than fully human mAbs.

Regeneron REGN14287 clinical trial is scheduled to launch in 2023, pending regulatory discussions. The phase 3 study clinical trial was last updated on July 29, 2022.

AZD5156 is an investigational, long-acting antibody combination of cilgavimab, a component of EVUSHELD, and a new long-acting mAb, AZD3152. AZD5156. The SUPERNOVA phase 3 study evaluates the safety and neutralizing activity of AZD5156 for the prevention of symptomatic COVID-19 in adults and adolescents 12 years of age.

Vyrologix (Leronlimab) is a humanized monoclonal antibody targeted against CCR5. The CCR5 receptor plays a central role in modulating immune cell trafficking to sites of inflammation.

Immunome, Inc. IMM-BCP-01 is a three-antibody cocktail targeting non-overlapping regions of the Spike protein. It elicits multi-modal activity in preclinical testing, including ACE2 and non-ACE2 dependent neutralization, and inducing natural viral clearance mechanisms, such as complement activation and phagocytosis.

Aridis Pharmaceuticals's AR-701 is a cocktail of two fully human immunoglobulins G1 (IgG1) mAbs, AR-703, and AR-720, each neutralizes coronaviruses using distinct mechanisms of action, namely inhibition of viral fusion and entry into human cells (AR-703) and blockage of viral binding to the human 'ACE2' receptor (AR-720). In addition, AR-703 binds to the 'S2' stalk region of spike proteins from beta coronaviruses.

Sorrento Therapeutics, Inc.'s STI-9167 neutralizing antibody was optimized to maximize protein stability and minimize interactions with host Fc gamma receptors.

Aerium Therapeutics P2G3 is a human mAb isolated from a previously infected and vaccinated, which displays picomolar-range neutralizing activity 'S2' against Omicron BA.1, BA.1.1, BA.2, and all other current variants.

ImmunoPrecise Antibodies Ltd.'s PolyTope® TATX-03 antibody cocktail has been requested by the F.D.A. and the European Medicines Agency to prepare comprehensive updates demonstrating the performance of PolyTope TATX-03 toward Omicron and other variants of concern.

Monoclonal Antibody Use By Pregnant Women

Original Research published on November 15, 2022, found in pregnant women with mild to moderate COVID-19 that adverse events after mAb treatment were mild and rare. There was no difference in obstetric-associated safety outcomes—another study found favorable results for hospitalized pregnant patients who received monoclonal antibodies due to COVID-19.

Monoclonal Antibody USe By Cancer Patients

The National Comprehensive Cancer Network® (NCCN) published expert consensus recommendations on vaccination and pre-exposure prophylaxis of COVID-19 in people with cancer, including information on using human mAbs, on January 4, 2022. In addition, the N.I.H. endorsed mAbsusede with certain cancer patients in 2022. UpToDate published an overview in Feb. 2023.

Covid Convalescent Plasma 2023

Covid convalescent plasma (C.C.P.) contains anti-Covid-19 antibodies harvested from people who recovered from COVID-19. Following transfusion, C.C.P. can effectively reduce hospitalizations in immunocompromised patients (JAMA, January 12, 2023). However, the current FDA-EUA (Dec. 2022) limits authorization to use C.C.P. products that are not mAbs.

SARS-CoV-2 Monoclonal Antibody News 2023

August 22, 2023 - Leonard S. Schleifer, M.D., Ph.D., Board Co-Chair, President, and Chief Executive Officer of Regeneron commented in a press release, "Although COVID-19 has moved to an endemic stage, many people – including those with immunocompromising conditions – continue to face exposure that impacts their everyday life and could cause serious health consequences. We believe Regeneron can once again apply our drug discovery and development expertise to help prevent disease in vulnerable populations. American biopharmaceutical companies developed remarkable COVID-19 therapeutics and vaccines in record time, successfully changing the pandemic's course. Wwe're gratified that the U.S. Government continues to support early research from this uniquely innovative industry."

February 13, 2023 - Tonix Pharmaceuticals Holding Corp. announced that it had exercised an option to obtain an exclusive license from Columbia University (N.Y.) for the development of a portfolio of fully human (TNX-3600) and murine (TNX-4100) mAbs for the treatment or prevention of SARS-CoV-2 infection. 

January 26, 2023 - U.S. F.D.A. announces Evusheld is not currently authorized for emergency use in the U.S.