Positive Initial Results Released For Regeneron’s Antibody Cocktail

The New England Journal of Medicine (NEJM) published initial clinical data from an ongoing seamless Phase 1/2/3 trial of the antibody cocktail casirivimab and imdevimab in non-hospitalized patients being treated for COVID-19.

In this interim analysis, the REGN-COV2 antibody cocktail reduced viral load, with a more significant effect on patients whose immune response had not yet been initiated or had a high viral load at baseline.

Casirivimab and imdevimab (formerly known as REGN-COV2 or REGEN-COV2) is a cocktail of two monoclonal antibodies (also known as REGN10933 and REGN10987, respectively) and was designed specifically to block the infectivity of SARS-CoV-2, the virus that causes COVID-19.

"The peer-reviewed NEJM publication of our first set of clinical data in recently infected COVID-19 patients showed that casirivimab and imdevimab effectively reduced viral load and the need for medically-attended visits, with the greatest benefit in patients who had not yet mounted their own effective immune response or had high viral load at baseline," said David Weinreich, M.D., Senior Vice President and Head of Global Clinical Development at Regeneron and lead author of the publication, in a press release.

"The investigational cocktail is now available to indicated high-risk U.S. patients under an Emergency Use Authorization, and we also continue a robust clinical development program."

To develop this novel medicine, Regeneron scientists evaluated thousands of fully-human antibodies produced by the company's VelocImmune® mice, which have been genetically modified to have a human immune system, as well as antibodies identified from humans who have recovered from COVID-19. 

The two potent, virus-neutralizing antibodies that form the cocktail bind non-competitively to the critical receptor binding domain of the virus's spike protein, diminishing mutant viruses' ability to escape treatment protects against spike variants that have arisen in the human population, as detailed in Science.

"These follow-on data provided the first definitive prospective evidence demonstrating anti-viral activity for a treatment regimen now available for COVID-19, and also further documented the ability of this treatment to decrease the need for further medical attention," added George D. Yancopoulos, M.D., Ph.D., President, and Chief Scientific Officer at Regeneron. 

"We are continuing to evaluate our antibody cocktail in this outpatient setting, as well as in late-stage trials in hospitalized patients and for prevention of infection, and will continue to share our findings as quickly as possible."

Regeneron previously announced the initial results featured in this NEJM publication from the Phase 1/2 portion of the trial that enrolled 275 patients randomized 1:1:1 to receive 8 grams casirivimab and imdevimab (high-dose, n=90), 2.4 grams casirivimab and imdevimab (low-dose, n=92) or placebo (n=93). Approximately 64% had one or more underlying risk factors for severe COVID-19, including obesity (more than 40%).

Regeneron also subsequently announced additional prospective results in a total of 799 patients from the trial. 

In both the initial descriptive analyses of 275 patients, as well as in the following prospective studies involving a total of 799 patients, a greater effect was observed in patients treated with the antibody cocktail who did not have SARS-CoV-2 antibodies at baseline ('sero-antibody-negative') or who had high viral load at baseline. 

As would be expected, a much higher proportion of sero-antibody-negative patients had high viral loads when they entered the trial. 

Additionally, a smaller proportion of antibody cocktail-treated patients required medically-attended visits due to COVID-19 (inclusive of hospitalizations, urgent care or emergency room visits, in-person physician or telemedicine visits) through day 29 compared to placebo; there was an even greater benefit on this endpoint among sero-antibody-negative patients.

In the initial 275 patients, rates of adverse events (AEs) were similar among groups. Serious AEs occurred in 2 placebo patients, 1 low-dose patient, and 0 high-dose patients. AEs included infusion-related reactions (1 placebo patient, 0 low-dose patients, 2 high-dose patients) and hypersensitivity reactions (2 placebo patients, 0 low-dose patients, 1 high-dose patient).

The antibody cocktail’s development and manufacturing have been funded in part with federal funds from BARDA under OT number: HHSO100201700020C. Data from the Phase 1/2/3 clinical trial supported an Emergency Use Authorization for casirivimab and imdevimab administered together, granted by the U.S. Food and Drug Administration (FDA) for the treatment of mild to moderate COVID-19 in patients 12 years of age and older and weighing at least 40 kg, who have received positive results of direct SARS-CoV-2 viral testing and are at high risk for progressing to severe COVID-19 and/or hospitalization. 

Regeneron continues to increase in-house production of casirivimab and imdevimab, and the company has partnered with Roche to increase the global supply beginning in 2021. Suppose the therapy proves safe and effective in clinical trials, and regulatory approvals are granted. In that case, Regeneron will manufacture and distribute it in the U.S. Roche will develop, manufacture, and distribute it outside of the U.S. Once both companies are at full manufacturing capacity in 2021, there are expected to be at least 2 million treatment doses available annually.

Casirivimab and imdevimab injection is an investigational combination therapy and has been authorized by the FDA for the emergency use described above. Casirivimab and imdevimab injection are not FDA approved for any use. The safety and effectiveness of casirivimab and imdevimab injection have not yet been established to treat COVID-19.

This authorized use is only for the duration of the declaration that circumstances exist justifying the authorization of the emergency use under section 564 (b)(1) of the Act, 21 U.S.C. § 360bbb-3(b) (1) unless the authorization is terminated or revoked sooner.

New York-based Regeneron is a leading biotechnology company that invents life-transforming medicines for people with serious diseases.

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