FDA Panel Narrowly Backs EUA for Merck’s COVID-19 Antiviral

In a 13-10 vote yesterday, an FDA advisory committee recommended that the FDA should grant Emergency Use Authorization (EUA) for molnupiravir, the antiviral pill co-developed by Merck and Ridgeback Biotherapeutics.

The expert panel narrowly endorsed giving the pill to adults with mild-to-moderate COVID-19 within five days of symptom onset who are at high risk of progressing to severe disease.

But even among members of the Antimicrobial Drugs Advisory Committee (AMDAC) who believed the pill’s benefits outweighed its risks, there were concerns about whether it should be given to pregnant women because of the lack of safety data for this population.

New data supplied by Merck from a late-stage trial showed that the pill reduced the risk of hospitalization or death by only 30 percent, rather than the almost 50 percent rate demonstrated in an earlier analysis (DID, Nov. 30).

Sankar Swaminathan, an infectious disease specialist at the University of Utah, reflected the opinion of most dissenting panelists when he noted that “the overall absolute effect in the total trial population was modest at best,” and that the possibility of birth defects “has not been adequately studied.”

W. David Hardy, an infectious disease specialist at Charles Drew University of Medicine and Science, said he found it troubling that molnupiravir’s efficacy decreased when more patients were added following the interim analysis. “I think we should all stop and acknowledge the whole reason we’re having this discussion [about pregnant women] is because the efficacy of this product is not overwhelmingly good,” he said.  

Panelists also noted that monoclonal antibodies from Regeneron and Eli Lilly have shown greater efficacy against COVID-19, although they acknowledged that those treatments are harder to administer because they are delivered via infusion or injection at a doctor’s office and can’t be given at home.

Members of the expert panel also expressed concerns that the pill might not be effective against the Omicron strain or future variants, or that it might even give rise to new variants by causing mutations to the SARS‑CoV‑2 spike protein. However, Merck said it believes the pill will be effective against the Omicron strain although it continues to evaluate the new variant.

The FDA is under no obligation to follow the advice of its advisory committees, but it generally does. If molnupiravir receives an EUA it would become the first antiviral pill to get the regulatory green light for treating COVID-19.

Pfizer filed an EUA request for its oral COVID-19 therapy, Paxlovid (PF-07321332; ritonavir), last month. Paxlovid has demonstrated considerably better efficacy than molnupiravir, cutting the risk of hospitalization and death by 89 percent vs. placebo in an interim analysis for a phase 2/3 study (DID, Nov. 19). ― Jason Scott