The Food and Drug Administration on Saturday granted emergency approval to the COVID-19 drug used last month to treat President Donald Trump, clearing the antibody-based treatment from Regeneron for use in patients at risk of severe disease or hospitalization.
The authorization, a special approval given during a public health emergency, is for Regeneron's REGEN-COV2, a combination regimen of two antibodies called casirivimab and imdevimab. The decision clears Regeneron's drug for use in patients aged 12 years or older whose COVID-19 symptoms are mild to moderate.
To be eligible for treatment, patients have to test positive for SARS-CoV-2 and be at "high risk" of their disease progressing. The risk factors specified by the agency include age of 65 years or older, or chronic underlying health conditions like high body mass index, diabetes, kidney or heart disease.
In a letter, the FDA noted REGEN-COV2 should be used "as soon as possible" after a positive test and within 10 days of the onset of symptoms. The key supportive evidence, the FDA said, was the drug's ability to reduce the number of medical visits — particularly hospitalizations and emergency room visits — within 28 days of treatment, compared to a placebo. Three percent of high-risk patients in clinical testing needed medical attention, versus 9% of placebo patients, although the rates are based on very small numbers.
The drug appears most effective in people who have high levels of virus and whose immune systems haven't mount a response. The agency did not, however, specifically mandate the testing that would be required to identify those patients.
Approval of Regeneron's drug comes two weeks after the FDA cleared a similar medicine from Eli Lilly, and as cases of COVID-19 and hospitalizations climb to new heights in the U.S. Early study results have suggested the treatments, made of synthetic antibodies that mimic the body's natural defenses, can help clear the coronavirus and keep people out of the hospital.
"Authorizing these monoclonal antibody therapies may help outpatients avoid hospitalization and alleviate the burden on our health care system," said FDA Commissioner Stephen Hahn in a statement. More than 83,000 Americans are currently hospitalized with COVID-19, according to The Atlantic's COVID tracking project.
But the evidence is not yet conclusive, and seem to indicate the drugs are only useful in treating people diagnosed with COVID-19 but whose symptoms remain mild. Lilly's treatment bamlanivimab — cleared for a similar group of patients — was removed from a government-sponsored study after it failed to help people who are already hospitalized. Regeneron, meanwhile, modified a study in hospitalized patients after a worrisome safety signal was seen in some of those who needed breathing support.
The agency, as a result, hasn't yet cleared either drug for those patients and noted the use of monoclonal antibody drugs may be tied to "worse clinical outcomes" when used after hospitalization. In its letter, the agency cited a few severe infusion reactions and a single case of anaphylaxis reaction in clinical testing of REGEN-COV2, though none of those cases occurred in the dose the FDA cleared.
Still, the treatment must be given in a hospital or clinic with access to drugs that can treat a severe infusion reaction. That requirement, along with the need for fast testing results to identify the right individuals for treatment, will likely make it difficult to get treatment to the right patients at the right time. Those logistical hurdles, combined with supply constraints and significant early promise vaccines have shown, make it unclear how big of a role antibody-based drugs will play in the coming months.
Already, hospitals are reportedly struggling with how to administer Lilly's drug, and whether to accept supply doled out by state health departments.
Antibody drugs have been viewed as a possible bridge to a vaccine since early in the pandemic. The drugs are meant to provide patients with a fast-acting, yet temporary defense to fight off COVID-19. They're also being tested as preventive medicines in people who have been exposed to the coronavirus. Their profile grew after President Donald Trump, former New Jersey Gov. Chris Christie, and most recently secretary of the Department of Housing and Urban Development Ben Carson received antibody drugs while being treated for COVID-19.
But antibody drugs didn't get nearly as much government funding support as coronavirus vaccines. That appears to have made it harder for developers to quickly scale up manufacturing. Regeneron, for instance, expects to have enough doses of REGEN-COV2 treat just 80,000 patients by the end of November, 200,000 by the first week of January and 300,000 by the end of that month.
Production will increase next year, as a partnership with Roche will help Regeneron make some 2 million doses annually beginning in 2021. Lilly has said it could manufacture about 1 million doses of bamlanivimab for use globally through the end of 2020.
The U.S. government pre-purchased 300,000 doses of each drug and is allocating them to states under the FDA's emergency authorization. Though patients won't be charged for doses secured by the U.S., they may need to pay costs related to treatment administration. Lilly set the price per dose of its drug at $1,250 outside of the U.S. supply agreement.
Regeneron hasn't yet announced a price, a company spokesperson said.
At the start of the pandemic, antibody drug developers believed their drugs might be an important option for elderly patients or those with weak immune systems, two groups less likely to respond vigorously to a vaccine. But early results from large studies of two coronavirus shots have surpassed expectations, showing 95% efficacy at protecting people from COVID-19. One of them, a vaccine from Pfizer and BioNTech, was found to be similarly effective in older adults, an encouraging result that makes it more likely other shots may protect those patients as well.
Multiple effective coronavirus vaccines, then, could be available for emergency use by the end of the year, and rolled out broadly in 2021. That may make antibody drugs less useful then first envisioned. In a statement, Regeneron chief scientific officer George Yancopoulos said he was "very encouraged" by the vaccine data produced so far, but "there remains a need to treat patients who develop COVID-19, especially as some may not have had access to or were not protected by vaccination."
Unlike Lilly's bamlanivimab, REGEN-COV2 is cocktail of two antibodies, a strategy meant to account for possible viral mutations and make it harder for the coronavirus to escape. Yancopoulos noted Regeneron hasn't seen any coronavirus variations that have been resistant to treatment in clinical testing.
Lilly is developing a combination treatment as well. Other antibody-based drugs from AstraZeneca and partners GlaxoSmithKline and Vir Biotechnology are also in late-stage testing.
Ned Pagliarulo contributed reporting.