Merck & Co.’s COVID-19 pill narrowly gained a key recommendation from advisers to U.S. regulators, after a lengthy debate about the safety of the potential game-changing treatment.
The Food and Drug Administration’s advisory committee voted 13-10 to back Merck’s antiviral drug molnupiravir, saying that while there were safety concerns about the pill, its potential benefits outweigh the risks.
The pill is intended to treat mild-to-moderate COVID-19 in adults at risk of developing severe illness. Merck developed the treatment with partner Ridgeback Biotherapeutics LP.
Merck’s shares rose 1.9% in late trading as the vote increased the likelihood that the treatment will be cleared for use in the U.S.
After the vote, several panel members said it was a difficult decision. Those who voted yes cited a need for a treatment like molnupiravir for high-risk individuals. But they cautioned that it shouldn’t be recommended for pregnant people, especially those in the first trimester. Panel members who voted no expressed concern about the lack of sufficient efficacy and safety data.
“Honestly, we were a little surprised,” said Daria Hazuda, vice president of Merck’s infectious diseases and vaccines division, in an interview after the vote, adding the drugmaker did a “thorough analysis” of the drug’s potential to do genetic damage.
Asked whether Merck planned to produce additional safety data to ensure regulators are comfortable authorizing the drug, Hazuda said, “we have to discuss with the agency if there are additional studies it feels is warranted.” But she believes that had the FDA wanted additional safety studies, the agency would have asked for that already.
The decision by the advisory committee comes amid rising concerns about a new coronavirus variant that is described by scientists as potentially of serious concern. Pfizer Inc. and partner BioNTech SE, Moderna Inc. and Johnson & Johnson are working to adapt their COVID-19 vaccines to address the omicron variant.
The FDA isn’t obligated to follow the recommendations of the panel, called the Antimicrobial Drugs Advisory Committee, though it typically does. A decision from the agency on whether to clear the pill could come soon after the meeting concludes Tuesday.
The pill could alter the fight against the pandemic by turning COVID-19 into an illness that is easily treated outside of a hospital setting. That may relieve the strain on health systems stretched thin by staffing shortages and rising infection levels.
Unlike other COVID-19 antivirals that are administered via intravenous infusion usually in hospitals or clinics, a five-day course of molnupiravir can be taken by patients at home.
Merck presented data from a study showing that its pill reduced the risk of hospitalization or death among adults with mild to moderate disease by 30%. That was lower than a previous estimate of 48%. The panel of advisers to the FDA peppered the drugmaker with questions about why the promising benefit molnupiravir demonstrated in the interim analysis decreased in the full study of all participants.
“What really changed in the overall study in the second half was the fact that the placebo group was apparently at lower risk of hospitalization and death,” Hazuda said.
With fewer patients receiving the placebo getting severely sick from the virus, it became more difficult for Merck to demonstrate as significant of a benefit with its treatment. “It’s not that the drug was less effective,” she said.
Hazuda said Merck did not have “a good explanation” as to why fewer participants in the placebo arm appeared to get very sick.
Molnupiravir works by introducing errors in genetic material to ultimately stop replication, which some experts have said may affect growing human cells.
For months, Merck has suggested that it’s confident that molnupiravir doesn’t pose long-term risk associated with systemic exposure to a DNA mutagen. The company had evaluated two distinct assays looking at the drug’s capacity to alter DNA in living organisms and found that the data looked clean.
Nicholas Kartsonis, senior vice president of clinical research for infectious diseases and vaccines at Merck Research Labs, had told Bloomberg he was “very impressed” by the drug’s safety results in an interview in March.
The FDA, however, raised questions about whether the treatment could cause birth defects, as well as bone and cartilage toxicity, and genetic mutations.
At the advisory committee hearing, Robert Heflich, the FDA’s director of the Division of Genetic and Molecular Toxicology, questioned the company’s perspective on the assays. “They really can’t tell if it’s positive or negative,” he said, referring to the results of the studies.
Separately, panel members expressed concern that molnupiravir could cause the virus to further mutate to evade immune defenses if patients didn’t complete their full treatment course.
“You’re purposely mutagenizing the virus,” said James Hildreth, president of Meharry Medical College, before the committee vote. “So with all respect, I think it’s incumbent upon you to make some effort to make an estimate of what is the likelihood of escape mutants occurring as a result of your drug.”
Merck’s Kartsonis stressed that the patients will be urged to take the full treatment course. That messaging isn’t just to “prevent evolution” of the virus, Kartsonis said, but also because it will ensure that patients get the greatest benefit from the treatment.
Hazuda added that the viruses naturally mutate to survive, and so “the best way to stop viral evolution is stop replication.” Treatment, she said, is the answer to both stopping replication in the body and transmission between people.
Regulators have already allowed Merck’s pill to be used in emergency treatment of adults in the European Union. It hasn’t been formally authorized for sale.
Pfizer is also pursuing FDA authorization for its own antiviral COVID-19 pill.
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