Discussion surrounding Merck’s newly-authorized COVID-19 pill, molnupiravir, has mostly concerned the risk it might pose to pregnant women. But some experts worry it could also lead to the outbreak of a new variant of the virus it’s designed to treat.
The Food and Drug Administration (FDA) granted emergency use authorization to two antiviral pills to treat COVID-19 this week, one from Pfizer (paxlovid) and another from Merck (molnupiravir). The Pfizer EUA was generally lacking in controversy, but the authorization of molnupiravir was far more contentious.
The FDA’s Antimicrobial Drugs Advisory Committee (ADAC) voted at the end of November to recommend authorization of molnupiravir, but it was by a narrow 13-10 margin. Even the members who voted in favor did so with qualifiers: some said the pill shouldn’t be given to pregnant women, and others were skeptical of its efficacy.
“I don’t think I would want to take this drug, not knowing the effect it could have on my unborn child,” Dr. Roblena Walker, CEO of public health non-profit EMAGAHA Inc. and ADAC member, said at the time. She voted yes.
Some of the members who voted against recommending authorization expressed more serious concerns, that rather than help solve the pandemic with its 30% efficacy rate, molnupiravir could cause the breakout of a new variant.
Molnupiravir works by triggering mutations in the virus of an infected individual, and those mutations go on to eventually kill the infection, Dr. Peter Weina told the Daily Caller. Weina, an infectious disease specialist and director of the Defense Health Agency, is an ADAC member who voted against recommending authorization.
“The drug works by mutating the organism, and this is an organism in which we have a lot of mutations creating problems for us already,” Weina said. “Just like influenza and just like a lot of viruses, there’s a baseline relatively high mutation rate in these viruses. The fact is that most mutations are probably lethal to the organism, but a couple of them are going to end up being beneficial for the organism, and we’ve seen that with the successive different variants that have come out.”
In other words, while the overwhelming majority of mutations triggered by molnupiravir will do their job and kill the virus, its not inconceivable that one of those mutations could be beneficial to COVID-19 and lead to another dangerous variant.
Weina wasn’t the only committee member with this concern. Dr. James E.K. Hildreth, president of Meharry Medical College, told The Washington Post he voted no for the same reason: “I voted no. It was an easy vote for me to vote no. … There were more questions than answers. I think the potential for this drug to drive some very challenging variants into the public is a major, major concern.”
Part of the EUA given to molnupiravir states that the drug should only be given if no viable alternative is available, such as Paxlovid. But it’s expected that supply of Merck’s drug will outpace Pfizer’s initially, meaning that the latter’s offering with an 89% efficacy rate won’t be as readily available.
“The number needed to treat for this particular drug was 34. What that means in real life is that you have to treat 34 people to get one good outcome. Another way of looking at it means that 33 people who get the drug aren’t necessarily gonna benefit from it,” Weina told the Daily Caller. “And those are 33 out of 34 people that are going to be mutating the virus that’s in them with no potential benefit.”
“100% of the people that are getting the organism, their viruses are mutating. That’s how the drug works and it ends up killing the virus,” he continued. “But the problem of course is that we don’t know how many of those viruses may potentially get a mutation that causes yet another variant out there. Maybe a variant our vaccines have absolutely no efficacy against. So I think the potential risk out there is quite high.”
Hildreth told the Post the odds of a new variant mutating from molnupiravir use may be low, but the potential downside is high. “Even if the probability is very low, 1 in 10,000 or 1 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,” he said.
The FDA’s own scientists aren’t as concerned though, and ultimately the agency decided after nearly a month of review to grant the pill its EUA. Patrick Harrington, the FDA’s senior virology reviewer, seemingly acknowledged the theoretical risk when addressing ADAC but downplayed it: “For molnupiravir to affect Sars-CoV-2 evolution beyond a treated individual, the variants would also have to be transmissible, and at this time we do not know if this is possible to a significant degree.”