The Food and Drug Administration’s (FDA) Antimicrobial Drugs Advisory Committee voted 13 to 10 in favor of authorizing the emergency use of molnupiravir, an investigational oral antiviral, for the treatment of mild to moderate COVID-19 in patients who are at high risk of progressing to severe disease or hospitalization.

Molnupiravir is an orally administered form of a ribonucleoside analogue that inhibits the replication of SARS-CoV-2. The Emergency Use Authorization (EUA) request included data from the phase 3 MOVe-OUT trial (ClinicalTrials.gov Identifier: NCT04575597), which investigated the efficacy and safety of molnupiravir in nonhospitalized patients 18 years of age and older with confirmed COVID-19 and symptom onset within 5 days prior to randomization.

Findings from a planned interim analysis that included 775 patients showed that treatment with molnupiravir reduced the risk of hospitalization or death by 48% (relative risk, 0.52; 95% CI, 0.33-0.80) compared with placebo. The final analysis of the MOVe-OUT trial, which included all enrolled patients (N=1433), showed that the treatment reduced the risk of hospitalization or death by 30% (relative risk, 0.70; 95% CI, 0.49-0.99).


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The most frequently reported drug-related adverse events were diarrhea, nausea, dizziness, and headache.

Concerns over potential embryo-fetal toxicity were raised during the meeting, as pregnant individuals were excluded from the trial. In the briefing document, it was reported that nonclinical reproductive toxicology studies demonstrated embryo-fetal toxicity, bone and cartilage-related formation findings, and mutagenicity. Based on these findings, the known and potential benefits of molnupiravir may not outweigh the known and potential risks in pregnant people.

An analysis of the data also showed treatment-emergent spike amino acid changes in some trial participants. “It remains unclear if the potential for [molnupiravir]-associated changes in the SARS-CoV-2 spike protein presents a public health risk, considering anticipated widespread use of [molnupiravir],” the Agency noted in the briefing documents.

If the EUA is authorized, the recommended dosage of molnupiravir would be 800mg (four 200mg capsules) taken orally every 12 hours for 5 days. Treatment would begin within 5 days of symptom onset. Molnupiravir would be the first oral drug authorized to treat mild to moderate COVID-19.

Although not bound by the committee’s recommendations, the FDA does take them into consideration when making decisions on approval.

References

  1. Merck and Ridgeback statement on positive FDA advisory committee vote for investigational oral antiviral molnupiravir for treatment of mild to moderate COVID-19 in high risk adults. News release. November 30, 2021. https://www.businesswire.com/news/home/20211130006127/en/Merck-and-Ridgeback-Statement-on-Positive-FDA-Advisory-Committee-Vote-for-Investigational-Oral-Antiviral-Molnupiravir-for-Treatment-of-Mild-to-Moderate-COVID-19-in-High-Risk-Adults.
  2. Antimicrobial Drugs Advisory Committee meeting. US Food and Drug Administration website. Accessed November 30, 2021. https://www.fda.gov/media/154418/download.

This article originally appeared on MPR