The antibody cocktail was given to US president Donald Trump in October as part of his treatment for COVID-19. It is the first COVID-19 combination therapy to receive an EUA from the FDA.
The initial doses produced by Regeneron will be distributed in the US: starting this month and covering up to 300,000 patients in total by the end of January. A partnership with Roche will take supply global in the first quarter of 2021 with at least 2 million treatment doses to be produced annually.
Treatment of mild to moderate cases
Casirivimab and imdevimab administered together was authorized by the FDA on Saturday [November 21] for the treatment of mild to moderate COVID-19 in adults, as well as in pediatric patients at least 12 years of age 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.
Under the EUA, the recommended dose is 1,200 mg of casirivimab and 1,200 mg of imdevimab (2,400 mg total) administered as a single intravenous infusion.
“The clinical evidence from Regeneron’s outpatient trial suggests that monoclonal antibodies such as casirivimab and imdevimab have the greatest benefit when given early after diagnosis and in patients who have not yet mounted their own immune response or who have high viral load,” explains Regeneron.
The cocktail is not authorized for use in COVID-19 patients who are hospitalized or require oxygen therapy.
The FDA's Commissioner, Stephen M. Hahn, M.D., said: “Authorizing these monoclonal antibody therapies may help outpatients avoid hospitalization and alleviate the burden on our health care system.
“As part of our Coronavirus Treatment Acceleration Program, the FDA uses every possible pathway to make new treatments available to patients as quickly as possible while continuing to study the safety and effectiveness of these treatments.”
The data supporting this EUA for casirivimab and imdevimab are based on a randomized, double-blind, placebo-controlled clinical trial in 799 non-hospitalized adults with mild to moderate COVID-19 symptoms. Patients received either a single intravenous infusion of 2,400mg casirivimab and imdevimab (1,200mg of each); 8,000mg casirivimab and imdevimab (4,000mg of each) or placebo within three days of a positive SARS-CoV-2 test.
"The prespecified primary endpoint for the trial was time-weighted average change in viral load from baseline," notes the FDA. as it announced the EUA "Viral load reduction in patients treated with casirivimab and imdevimab was larger than in patients treated with placebo at day seven.
"However, the most important evidence that casirivimab and imdevimab administered together may be effective came from the predefined secondary endpoint of medically attended visits related to COVID-19, particularly hospitalizations and emergency room visits within 28 days after treatment.
"For patients at high risk for disease progression, hospitalizations and emergency room visits occurred in 3% of casirivimab and imdevimab-treated patients on average compared to 9% in placebo-treated patients. The effects on viral load, reduction in hospitalizations and ER visits were similar in patients receiving either of the two casirivimab and imdevimab doses."
How it works
Casirivimab and imdevimab injection is a cocktail of two monoclonal antibodies (also known as REGN10933 and REGN10987, respectively) and was designed specifically to block infectivity of SARS-CoV-2, the virus that causes 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, which diminishes the ability of mutant viruses to escape treatment and protects against spike variants that have arisen in the human population
The development and manufacturing of the antibody cocktail has been funded in part with federal funds from BARDA.
The FDA grants Emergency Use Authorization to medicines that may help diagnose, treat or prevent a life-threatening disease when adequate and approved alternatives are not available. The EUA is temporary and does not take the place of a formal biologics license application (BLA) submission review and approval process.
Ramping up production
Regeneron notes that demand is likely to exceed supply initially, with treatment for around 80,000 patients expected to be ready by the end of the month; meeting needs for around 200,000 patients by the first week of January and 300,000 in total by the end of January.
An agreement under Operation Warp Speed will see Regeneron dedicate the initial supply to the US Government, which will allocate the antibody cocktail on the basis of number of COVID-19 cases per state. It will be provided at no cost to patients, although healthcare facilities may charge fees related to administration.
With the EUA under its belt, Regeneron will immediately begin shipping doses to national distributor Amerisource Bergen, who will distribute the therapy as directed by the government.
In the first quarter of 2021, Regeneron will ramp up availability globally through a collaboration with Roche (Regeneron will continue to produce the antibody cocktail in the US with Roche developing, manufacturing and distributing outside the US).
Once both companies are at full manufacturing capacity next year, they expect to produce at least 2 million treatment doses a year.
Regeneron's casirivimab and imdevimab antibody cocktail is the first combination therapy to receive a COVID-19 EUA from the FDA. Earlier this month, Lilly's bamlanivimab (LY-CoV555) antibody became the first monoclonal antibody to receive an EUA from the FDA; which it has just followed with an EUA from Canada and strategic manufacturing partnership with South Korea's Samsung Biologics to expand supply globally.