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Monoclonal antibodies cut risk of dying from COVID-19—but only in some patients

Regeneron’s antibodies were studied in a clinical trial in outpatients in Arizona in 2020. Now, the RECOVERY study has found that the therapy reduces mortality in some hospitalized patients wtih severe diasease.

Adriana Zehbrauskas/The New York Times via Redux

Science’s COVID-19 reporting is supported by the Heising-Simons Foundation.

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 a fifth among those who did not produce antibodies themselves. A paper with the results will be made available on medRxiv 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 be reduce mortalitydeom 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 were demonstrated to save the lives of severely ill patients in the hospital. The RECOVERY trial started evaluating Regeneron’s cocktail in mid-September. 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 an 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.

The Regeneron cocktail received a lot of attention when U.S. President Donald Trump received it during his bout with COVID-19 in October 2020. Although it’s not clear whether Trump’s immune system produced antibodies, the new results suggest the treatment may have helped save his life, says Topol: “Who knows what might have happened at his age, with his morbid obesity and all the other risk factors that he had.”

Although it received an emergency use authorization from the Food and Drug Administration in November 2020—and the U.S. government bought 1.5 million doses— Regeneron’s therapy has not been widely used in the United States, Topol says. “This is just sitting on shelves,” he says. “I think [the RECOVERY trial] is going to wake people up as to the benefit.”

But doctors will have to determine which patients fail to produce antibodies. “I think this isn’t a complicated test to run, it just needs to be done,” says Martin Landray of the University of Oxford, one of RECOVERY’s principal investigators.

A bigger challenge may be cost. “We anticipate, but we don’t know this, that they may be around £1000 or £2000 per treatment,” RECOVERY co-investigator Peter Horby said at a press conference on Tuesday. That might put the therapy and many similar ones in the pipeline out of reach for most people living in developing countries, which also have far fewer COVID-19 vaccine doses than rich countries.  Access to antibody drugs in general has been particularly unequal across the globe, says Lindsay Keir, a pediatrician who co-authored a Wellcome Trust report on global access to such treatments released last year. “Antibodies that we have benefited from in high income countries for 20, 30 years, still aren’t available in many countries,” Keir says.

The inequity is a “scandal,” Horby says. “There really must be an initiative to make these drugs accessible, and that requires two things: They have to be available, which means we have to scale up manufacturing, and they have to be affordable, which means we have to reduce the prices.”

Source: Science Mag