FDA Vaccine Committee Will Review Merck’s Oral COVID-19 Pill

Molnupiravir, the controversial COVID-19 oral antiviral made by Merck and subsidiary Ridgeback Therapeutics, will have its day in committee, the FDA has announced.

Responding to the companies’ recent request for Emergency Use Authorization (EUA), the agency has asked its Vaccinesand Related Biological Products Advisory Committee to review all the data at a special meeting on Nov. 30.

“We believe that, in this instance, a public discussion of these data with the agency’s advisory committee will help ensure clear understanding of the scientific data and information that the FDA is evaluating to make a decision about whether to authorize this treatment for emergency use,” said Patrizia Cavazzoni, director of the FDA’s Center for Drug Evaluation and Research.

Merck will present positive interim data from its phase 3 MOVe-OUT study of nonhospitalized adults with mild-to-moderate COVID-19 at risk of progression to severe disease, including hospitalization or death. The drug cut the risk of hospitalization or death in this population by 50 percent; 7.3 percent of patients given the molnupiravir were either hospitalized or died (28/385), compared with 14.1 percent of placebo-treated patients (53/377). By day 29 of treatment, there were no deaths in the molnupiravir group; eight had died in the placebo-treated group.

An independent data monitoring committee recommended that Merck stop the study early due to positive results, and the FDA agreed.

The decision to go through an advisory committee process rather than grant immediate EUA hints at some of molnupiravir’s controversy. In May, a team from the University of Chapel Hill, N.C., found that the drug induced mutations in hamster cells. Coupled with unfounded yet common beliefs swirling around COVID-19 vaccines’ negative effects on reproduction, this finding will likely set the stage for a lively public discussion.

A team of Merck scientists refuted the Chapel Hill group’s findings in an open letter in the Journal of Infectious Diseases. Merck did find some mutagenic properties in cell cultures, Sean Troth and his colleagues reported, but not in its live animal studies, including two in rodents and one in pigs. Mutation rates in treated animals were similar to naturally occurring rates. Additionally, the team said, “These in vivo mutation assays evaluated [the drug] at doses and durations significantly greater than those being used in the clinic.”

Read the Chapel Hill study here: bit.ly/3lLgEok.

Read Merck’s open letter response here: bit.ly/3AQ1HFE. — Michele G. Sullivan