Monoclonal Antibody Treatment
Monoclonal Antibody Treatment Description
The main target of SARS-CoV-2 virus-neutralizing monoclonal antibodies is the surface spike glycoprotein that mediates viral entry into host cells. Essentially all monoclonal antibodies of interest target this protein.
These agents are often created by identifying pathogen-specific B cells of patients who have recently recovered from COVID-19 or by immunizing mice genetically modified to have a humanized immune system and harvesting effective antibodies from them.
Monoclonal antibodies have singular activity against a predetermined target. Therefore, they differ from convalescent plasma, which consists of polyclonal antibodies in serum derived from patients convalescing from virus infection.
Monoclonal Antibodies Authorized
In the U.S.A, four anti-SARS-CoV-2 monoclonal antibody products are Authorized to treat non-hospitalized patients with mild to moderate COVID-19. The U.S. HHS began allocating these antibody products to states on September 13, 2021.
Regeneron's (NASDAQ: REGN) REGEN-COV (Casirivimab and Imdevimab) is potent, virus-neutralizing antibodies that form the REGEN-COV Antibody Cocktail 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, as detailed in Science, published on August 21, 2020.
Eli Lilly's (NYSE: LLY) Bamlanivimab (LY-CoV555) neutralizing IgG1 monoclonal antibody (mAb) is directed against the spike protein SARS-CoV-2 coronavirus. Bamlanivimab was designed to block viral attachment and entry into human cells, thus neutralizing the virus, potentially preventing and treating COVID-19. In addition, a second Lilly antibody, LY-CoV016, which binds a different epitope in the SARS-CoV-2 spike region, has been added to the BLAZE-1 clinical trial. Etesevimab (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 block the binding of the virus to the ACE2 host cell surface receptor.
Vir Biotechnology, Inc.'s Sotrovimab (VIR-7831, GSK4182136) (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. Vir Biotechnology's (NASDAQ: VIR) antibody binds to an epitope on SARS-CoV-2 shared with SARS-CoV-1. The data that support the EUA for sotrovimab come from the Phase 3 COMET-ICE trial, which included outpatients with mild to moderate COVID-19 who were at high risk for progression to severe disease and/or hospitalization.
Actemra (Tocilizumab) is indicated for adults with moderate-to-severe active rheumatoid arthritis with inadequate response to 1 or more disease-modifying antirheumatic drugs. On June 24, 2021, the FDA issued a Fact Sheet for Health Care Providers EUA of Tocilizumab for COVID-19.
Note: Review the Antiviral Resistance information in Section 15 of the authorized Fact Sheets for each monoclonal antibody therapy available under a EUA for details regarding specific variants and resistance. It would be best to refer to the CDC website and information from state and local health authorities regarding reports of viral variants of importance in their region to guide treatment decisions.
Monoclonal Antibodies - Experimental
Brii Biosciences Limited - BRII-196/BRII-198 are non-competing SARS-CoV-2 monoclonal neutralizing antibodies derived from convalesced COVID-19 patients. They have been specifically engineered to reduce the risk of antibody-dependent enhancement and prolong the plasma half-lives for potentially more durable treatment effect. In addition, their non-overlapping epitope binding regions provide a high degree of neutralization activity against SARS-CoV-2. Authorizations are pending in the USA and China.
AstraZeneca - Positive high-level results from the PROVENT Phase III pre-exposure prophylaxis trial showed AstraZeneca's COVID-19 Antibody AZD7442 achieved a statistically significant reduction in the incidence of symptomatic COVID-19, the trial's primary endpoint.
AutoAntibodies and SARS-CoV-2
Nature Communications published a study on September 14, 2021: New-onset IgG autoantibodies in hospitalized patients with COVID-19. These researchers concluded 'that the SARS-CoV-2 virus causes the development of new-onset IgG autoantibodies in a significant proportion of hospitalized COVID-19 patients and is positively correlated with immune responses SARS-CoV-2 proteins. Thus, autoantibodies can be early harbingers of full-blown autoimmune disease.' Furthermore, "To an extent never seen for any other acute infectious disease, these four studies collectively provide a molecular and immunological explanation for about 20 percent of critical cases." Moreover, these autoantibodies are found even in uninfected individuals, suggesting that they cause, rather than an effect, severe COVID-19.
Monoclonal Antibodies News
September 24, 2021 - The WHO issued a conditional recommendation for Regeneron's monoclonal antibody cocktail REGEN-COV (casirimivab and imdevimab) for patients with nonsevere COVID-19 who are at high risk for hospitalization and for people who have severe and critical infections who have no antibodies to SARS-COV-2.
September 20, 2021 - Gov. Ron DeSantis Tweeted: 'Since Florida opened monoclonal antibody treatment sites in August: +100,000 Floridians have received treatments; COVID hospital admissions have fallen by over 60%; COVID hospital census has declined for 28 consecutive days; ER visits for COVID have declined by over 70%.
September 20, 2021 - Texas Governor Greg Abbott announced that the Texas Division of Emergency Management would expand operations at an active COVID-19 therapeutic infusion center in Segu in partnership with local officials. The expansion is expected to double the number of daily infusions from 25-30 to approximately fifty.
September 19, 2021 - BreatheMD.com posted unverified, self-reported Monoclonal Antibody Treatment results based on 410 patients' responses. About 97% of Regen-CoV patients would recommend the treatment to a loved one, and 83% did not report side effects.
September 16, 2021 - The U.S FDA confirmed it concluded that revising this EUA is appropriate to protect public health or safety under section 564(g)(2) of the Act; FDA is reissuing the August 27, 2021 letter in its entirety also to authorize bamlanivimab and etesevimab administered together for emergency use as post-exposure prophylaxis in certain adults and pediatric individuals.
September 9, 2021 - The European Medicines Agency published updated safety reports for potential 19 antibody treatments for COVID-19 patients in the European Union.
August 26, 2021 - UK medicines regulator has approved Ronapreve (REGEN-COV) for COVID-19 treatment. Ronapreve is administered as an infusion or multiple injections. This product is already licensed for emergency use in more than 20 countries – including the US, Japan, and India.
August 25, 2021 - Brii Biosciences (HKG: 2137) announced positive results from the NIAID-sponsored Activ-2 trial in outpatients. "We are thrilled to announce the interim Phase 3 results from ACTIV-2, which demonstrate a significant reduction in the endpoint of hospitalizations or death among non-hospitalized people with mild COVID-19 who were treated with BRII-196/BRII-198," said Teresa H. Evering, M.D., M.S., Weill Cornell Medicine, co-lead investigator of BRII-196/BRII-198 in ACTIV-2.
Note: This content is aggregated from various sources and fact-check by healthcare providers.