Research report on Monoclonal antibodies: They cut risk of dying from COVID-19—but only in some patients

Monoclonal antibodies cut risk of dying from COVID-19—but only in some patients Regeneron cocktail reduces mortality by 20% in those who don’t produce antibodies themselves, RECOVERY trial shows Science | AAAS

The world’s largest trial of COVID-19 therapeutics has for the first time produced convincing evidence that a therapy that directly attacks the virus can save hospitalized patients from death. A combination of antibodies called casirivimab and imdevimab, produced by Regeneron, did not lower mortality when all patients in the study were taken together, investigators of the United Kingdom’s Recovery trial announced today—but it reduced deaths by one-fifth among those who did not produce antibodies themselves. A paper with the results will be made available on the medRxiv preprint server later today, the researchers say.

“Here you have really the first direct SARS-CoV-2 drug,” says Eric Topol, director of the Scripps Research Translational Institute. Two drugs previously shown to reduce mortality from COVID-19 were developed for other diseases and work by dampening an overactive immune response, which is “kind of an indirect strategy,” Topol says.

But Regeneron’s antibodies, which attach to the receptor-binding domain of the spike protein and prevent the virus from entering cells, are expensive and not widely available, and quickly identifying patients that benefit from it may be a challenge.

Researchers have developed several monoclonal antibodies against SARS-CoV-2, with mixed results. Some, including Regeneron’s, have shown some positive effects on disease progression in outpatients, but none was demonstrated to save the lives of severely ill patients in the hospital. The Recovery trial started to evaluate Regeneron’s cocktail in mid-September 2020. By late May, 9785 patients had been randomly allocated to receive either the usual care in the United Kingdom or the usual care plus a one-time infusion of the two antibodies, a procedure that takes roughly 1 hour.

About one-third of the patients were seronegative when they entered the trial, meaning they did not produce antibodies themselves. That includes people with underlying health conditions that weaken their immune system, but also people who, for unclear reasons, are unable to produce antibodies early on. In this group, 30% of patients given standard care died, versus 24% of those who received the antibody cocktail. That translates to six lives saved for every 100 such patients treated with the drug. ...

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