Merck and Ridgeback’s recent report that its antiviral molnupiravir wasn’t nearly as effective as previously indicated put a damper on enthusiasm that a game-changing oral treatment for COVID-19 was near. It also drew questions at the FDA on whether to approve the pill on an emergency use basis at all.
On Tuesday, an FDA advisory committee voted by the narrow margin of 13-10 to endorse the use of molnupiravir. The recommendation comes despite a host of concerns, including over the efficacy and safety of the antiviral medicine.
“In my many years of chairing this committee, this is the first meeting that has gone over (its time limit), which I think speaks to the complexity of the issues,” said Lindsey Baden, M.D., of the Brigham and Women’s Hospital of Boston.
The endorsement covers adults with mild-to-moderate COVID-19 who are within five days of symptom onset and are at high risk of developing a severe form of the disease.
Advisory committee members who voted on both sides of the molnupiravir question said that they would support revoking the nod for Merck and Ridgeback’s drug if another oral treatment was approved that showed a superior efficacy and safety profile.
It will be up to the FDA and CDC to sign off on the recommendation from the Antimicrobial Drugs Advisory Committee before molnupiravir can be cleared for use in patients. If that should happen, U.S. officials have already agreed to purchase more than 3 million courses of the treatment.
Merck could not explain why the same phase 3 study produced differing results roughly seven weeks apart, drawing consternation from the committee members. Interim data issued in late October from a study of more than 700 participants showed that molnupiravir reduced the risk of hospitalization and death by 48% over placebo. A longer-term look however showed that molnupiravir reduced the risks by just 30%.
Many advisory committee members who voted not to recommend approval pointed to a minimal efficacy advantage. The rates of hospitalization or death in the molnupiravir and placebo arms were 6.8% and 9.7%, respectively.
“I thought the overall absolute effect in the total trial population was modest at best,” said Sankar Swaminathan, M.D., of the University of Utah. “Given the large potential population effected, the risk of widespread effect on potential birth defects—especially delayed effects on the male—have not been adequately studied.”
Michael Green, M.D., of the University of Pittsburgh, said he voted to recommend molnupiravir in part because of a potential lack of availability of alternative therapies as coronavirus variants emerge.
“I would use it in high-risk, non-vaccinated individuals,” Green said.
Much of the discussion centered on the questionable safety of the treatment on pregnant women and other women of childbearing age. In pregnant rats, molnupiravir killed embryos.
If approved, molnupiravir will become the first oral treatment for COVID-19. Pfizer has also asked the FDA to approve its oral candidate Paxlovid, which was shown to reduce the risk of hospitalization and death by 89%.