By IDSE News Staff
The FDA granted an emergency use authorization for molnupiravir (Merck/Ridgeback Biotherapeutics) to treat mild to moderate COVID-19 in adults who are at high risk for progression to severe disease, and for whom alternative treatments are not accessible or clinically appropriate.
Molnupiravir is not authorized for use in patients who are younger than 18 years of age, for initiation of treatment in patients hospitalized due to COVID-19, for use for longer than five consecutive days, or for pre-exposure or post-exposure prophylaxis for prevention of COVID-19.
Molnupiravir should be administered as soon as possible after a diagnosis of COVID-19 has been made, and within five days of symptom onset. The recommended dose for molnupiravir is 800 mg (four 200 mg capsules) taken orally every 12 hours for five days, with or without food. The FDA said the full five-day treatment course should be taken to maximize viral clearance and minimize transmission of SARS-CoV-2.
“Today’s authorization provides an additional treatment option against the COVID-19 virus in the form of a pill that can be taken orally. Molnupiravir is limited to situations where other FDA-authorized treatments for COVID-19 are inaccessible or are not clinically appropriate and will be a useful treatment option for some patients with COVID-19 at high risk of hospitalization or death,” said Patrizia Cavazzoni, MD, the director of the FDA’s Center for Drug Evaluation and Research. “As new variants of the virus continue to emerge, it is crucial to expand the country’s arsenal of COVID-19 therapies using emergency use authorization, while continuing to generate additional data on their safety and effectiveness.”
Molnupiravir works by introducing errors into the SARS-CoV-2 virus’ genetic code, which prevents viral replication.
The authorization is based on the Phase 3 MOVe-OUT trial, which evaluated molnupiravir 800 mg twice-daily in non-hospitalized adult patients who were unvaccinated against SARS-CoV-2, had laboratory-confirmed SARS-CoV-2 infection, symptom onset within five days of study randomization, and at least one risk factor associated with poor disease outcomes (e.g., heart disease, diabetes).
In analyses from all randomized patients (n=1,433), molnupiravir reduced the risk of hospitalization or death: 9.7% (68/699) of patients in the placebo group were hospitalized or died compared with 6.8% (48/709) of patients who received molnupiravir, for an absolute risk reduction of 3% (95% CI: 0.1, 5.9). Nine deaths were reported in the placebo group, and one in the molnupiravir group.
The determination of primary efficacy was based on a planned interim analysis of 762 patients. At the interim analysis, treatment with molnupiravir significantly reduced hospitalizations and death through Day 29 following randomization: 14.1% (53/377) of patients in the placebo group were hospitalized or died, compared with 7.3% (28/385) of patients who received molnupiravir.
The most common adverse reactions (AEs) were diarrhea, nausea and dizziness. Discontinuation of study intervention due to an AE occurred in 1% of people receiving molnupiravir and 3% receiving placebo. Serious AEs occurred in 7% of people receiving molnupiravir and 10% receiving placebo; most serious AEs were COVID-19 related. Molnupiravir is not recommended for use in patients who are pregnant. Based on findings from animal reproduction studies, molnupiravir may cause fetal harm when administered to pregnant individuals.
“Based on the strong science behind molnupiravir, a single oral medicine that interrupts replication of the SARS-CoV-2 virus, with data demonstrating a significant reduction in the risk of hospitalizations and deaths, molnupiravir has the potential to become an important tool for health care professionals and appropriate patients,” said Dean Y. Li, PhD, the president, Merck Research Laboratories.
Molnupiravir is not recommended for use in patients who are pregnant. Based on findings from animal reproduction studies, molnupiravir may cause fetal harm when administered to pregnant individuals.
Merck anticipates that it will begin shipping molnupiravir to AmerisourceBergen, the sole distributor of molnupiravir, within days. Merck has agreed to supply approximately 3.1 million courses of molnupiravir to the federal government.
Molnupiravir is also being evaluated for post-exposure prophylaxis in MOVe-AHEAD, a global, multicenter, randomized, double-blind, placebo-controlled Phase 3 study, which is evaluating the efficacy and safety of molnupiravir in preventing the spread of COVID-19 within households. Molnupiravir is not authorized for pre-exposure or post-exposure prophylaxis for prevention of COVID-19.
