Outside advisers to the U.S. Food and Drug Administration (FDA) on Tuesday narrowly voted to recommend the agency grant emergency use authorization (EUA) for a drug from Merck and Ridgeback Biotherapeutics to treat COVID-19, called molnupiravir.
Members of the FDA’s Antimicrobial Drugs Advisory Committee voted 13 for and 10 against the EUA for molnupiravir, agreeing with the idea that the drug’s benefits outweigh its potential risks, including potential birth defects if used during pregnancy.
While the FDA does not have to follow the advisers’ recommendation, it usually does. It will now consider the committee’s recommendation.
The drug is intended for use at home by adults with mild to moderate COVID-19 who are at high risk of developing severe disease. The drug is taken orally in pill form, twice a day for five days, within five days of symptoms onset.
Concerns of Triggering New Variants
Molnupiravir works by causing errors in the SARS-CoV-2 coronavirus’s genetic code to stop it from replicating. Specifically, molnupiravir targets part of the virus called the RNA polymerase.
That genetic effect has raised concerns that the drug could trigger more virulent strains of the CCP (Chinese Communist Party) virus, another name for SARS-CoV-2.
FDA regulators said Tuesday that the risk is theoretical, but many panelists said it should be carefully tracked in follow-up studies.
If granted the EUA, Merck’s antiviral pill would become the first at-home treatment for the CCP virus authorized by the FDA. The exact segment of the population who would be eligible to use the drug would need to be defined by the agency.
Merck published data last week suggesting that the antiviral pill showed a 30 percent relative risk reduction in hospitalizations and deaths in patients with early COVID-19 symptoms at high risk of disease progression. The results meant the drug is less effective than previously reported in October, at a relative risk reduction of 48 percent.
The results haven’t yet been peer-reviewed or published in a scientific journal.
According to Merck, in the trial, nine deaths were reported in the placebo group, and one in the molnupiravir group. Several members on the advisory panel said the reduced number of deaths in people who received molnupiravir in the trial convinced them to vote to recommend authorization.
“COVID-19 is still an emergency situation,” said committee member Dr. David Hardy, who voted yes. “There is a need for something like this. This is the first opportunity that an oral outpatient medication for mildly symptomatic to moderately symptomatic persons would be available, although I do have questions about its overall longer-term efficacy.”
Concerns of Birth Defects
Both FDA staff scientists and Merck have suggested the drug should not be recommended during pregnancy. Earlier Tuesday, FDA scientists told the panelists that company studies in rats showed the drug caused birth defects when given at very high doses. FDA staffers concluded the data “suggest that molnupiravir may cause fetal harm when administered to pregnant individuals.”
“Given the large potential population affected, the risk of widespread effects on potential birth defects has not been adequately studied,” said Dr. Sankar Swaminathan of the University of Utah School of Medicine, who voted against the drug.
Panelists did not say the drug should never be given during pregnancy, but did recommended it only be taken in rare circumstances—for example, when other treatments are not available.
“I don’t think you can ethically say it’s OK to give this drug in pregnancy, obviously,” Dr. Janet Cragan of the Centers for Disease Control and Prevention, a panelist, said during the discussions. “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.”
Roy Baynes, Merck’s chief medical officer, told STAT News after the panel vote that the decision to use the drug should be made by doctors.
“We would not recommend its use in pregnancy and we would also recommend contraception in women of childbearing age,” he said. “But I think the idea here is that ultimately the physician is the best position to determine the relative risk benefit for their patients.”
The U.S. federal government has contracted to buy 3.1 million courses of molnupiravir for $2.2 billion, which is about $700 per treatment course.
By comparison, the United States paid around $20 a dose for its supply of the two-dose Pfizer/BioNTech vaccine.
Dr. Dean Y. Li, Merck’s executive vice president and president, in a statement called the FDA advisory panel’s vote “a critical step toward bringing this promising oral medicine for COVID-19 to appropriate patients in the U.S.”
Wendy Holman, chief executive officer of Ridgeback Biotherapeutics, said in a statement, “We are one step closer to being able to add molnupiravir to the tools that we have—in addition to vaccines—that can be available and accessible to help fight COVID-19.
“Importantly, our data show activity against the most prevalent variants today, and molnupiravir was studied as a monotherapy with no drug-drug interactions observed to date.”
Another potential oral antiviral COVID-19 treatment from Pfizer, called Paxlovid, is also being considered for authorization by the FDA. The pill showed an 89 percent relative reduction in hospitalizations and deaths in its clinical trial.
The Associated Press and Reuters contributed to this report.