A panel of the Food and Drug Administration's outside drug advisers voted narrowly Tuesday to endorse allowing antiviral pills developed by Merck and Ridgeback Biotherapeutics to be prescribed for COVID-19, following an hours-long meeting mulling the benefits and risks of molnupiravir to treat the disease in high-risk adults.
While not binding, the vote by the FDA's Antimicrobial Drugs Advisory Committee could clear the way for the agency to grant emergency use authorization for adults, as the United Kingdom has already done. Some 3.1 million courses of Merck's five-day treatment have been purchased for distribution by the Biden administration, if the pill is greenlighted.
"I voted yes because COVID-19 is still an emergency situation," Dr. W. David Hardy, a scientist at Charles Drew University School of Medicine and Science and one of the committee members, said following the vote.
The committee's narrow backing, 13 votes in favor and 10 votes against, followed a day-long meeting of the committee questioning the balance of benefits and potential risks of the drug, given other COVID-19 treatments that have proven effective so far in aiding Americans sickened by the virus.
"As a frontline clinician, in treating patients both inpatient and outpatient, there is a need for something like this. This is the first opportunity that an oral outpatient medication for mildly symptomatic to moderate symptomatic persons would be available," Hardy said.
Molnupiravir works by trying to randomly create mistakes in SARS-CoV-2's efforts to copy itself through the body's cells, leading to an accumulation of errors that can stunt the replication of the virus.
Early results announced by Merck from its trial had touted a steep 50% drop in the risk of hospitalization or death, treating adults at risk of worse COVID-19 symptoms within days after they were diagnosed. But later data announced by Merck suggested the benefits of the drug were more modest in the company's trials, reducing the risk by just 30% compared to a placebo.
Merck argued their pill was still needed despite the widespread deployment of effective monoclonal antibodies, which are administered largely through resource-intensive infusion sites.
Merck's scientists said that molnupiravir had also proven safe for adults in the study with no signs of worrying side effects.
"As new variants emerge, some monoclonal antibodies may become less effective due to mutations in the spike protein which may alter the antibody binding site," Merck's Dr. Sean Curtis told the panel.
The FDA is not yet recommending pregnant Americans can take Merck's antiviral given concerns seen in Merck's animal testing of molnupiravir suggesting that it might affect the development of the child. Children will also not be authorized to receive the pills.
However, the agency asked the panel to discuss whether there were scenarios where molnupiravir could be permitted for Americans who are pregnant or might become pregnant, given the heightened risk of severe COVID-19 in pregnancy.
"I don't think you can ethically say it's okay to give this drug in pregnancy, obviously, but at the same time, I'm not sure you can ethically tell a pregnant woman who has COVID-19 that she can't have the drug if she's decided that's what she needs," said Dr. Janet Cragan, a medical officer with the CDC and one of the panel's advisers.
The advisers also grappled with the rare risk that the drug's mechanism of triggering new mutations of the virus might lead to a new variant of concern from SARS-CoV-2, especially in immunocompromised patients who might harbor and spread error-riddled copies of the virus for weeks after the treatment ends or people who do not hew closely to prescriptions to take all five days of pills.
"Even if the probability is very low, one in 10,000 to one in 100,000, that this drug would induce an escape mutant for which the vaccines we have do not cover, that would be catastrophic for the whole world actually," said Dr. James Hildreth, one of the panel's advisers
Merck's scientists acknowledged they did not have the data to accurately estimate the risk that might occur, but pointed out that none of the people who took the pills appeared infectious after they were treated with molnupiravir.
"There is a substantial amount of mutations emerging from natural infection which dwarfs what is done by this agent. But as pointed out by one of the committee members, it depends how much of this is used, how widely, with what level of compliance," said Dr. Lindsey Baden, the panel's chair.
Merck is not the only company pursuing the FDA's sign-off on an antiviral for COVID-19. The Biden administration inked a deal earlier this month for Pfizer's Paxlovid pills too, which early results showed a 90% reduction in risk and uses a different mechanism than Merck's pill to try and simply to block the replication of the virus.
"I think that, if an alternative agent comes along with better efficacy and fewer safety concerns, that this EUA should be immediately reconsidered," said Dr. Richard Murphy, a Veterans Affairs physician on the committee.
The FDA is unlikely to convene a meeting of its advisers to consider Pfizer's drug, the company's top scientists have speculated, given the lower risks posed by Paxlovid. The FDA declined to comment on whether it planned to convene a meeting before authorizing Pfizer's pills.
"We don't think that there is at all the same type of risk for these drugs and, as anticipated, the tolerability profile was very good," Pfizer's Dr. Mikael Dolsten said at a recent conference with investors hosted by Wolfe Research.
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