Molnupiravir is an oral antiviral drug that has been shown to decrease risk of hospitalization or death at 29 days in patients with mild to moderate COVID-19 who are at risk for progression to severe disease.
Why is this important?
As the pandemic continues, we continue to seek effective treatments for COVID-19, and this trial studied the efficacy and safety of molnupiravir as an agent to treat outpatients with mild to moderate COVID-19 at risk of progression to severe disease.
Molnupiravir is a nucleoside analog that inhibits SARS-CoV-2 replication and increases mutations in viral RNA. The MOVe-Out Trial was a phase 3, double-blind randomized controlled trial that evaluating efficacy and safety of treatment with molnupiravir started within 5 days of symptom onset. The trial included non-hospitalized, unvaccinated adults with mild to moderate, Covid-19 with at least one risk factor for progression to severe disease. These included age > 60 years, active cancer, chronic kidney disease, COPD, obesity (BMI ≥30), serious heart conditions, diabetes mellitus.
The trial excluded pregnant women or those unwilling to use contraception during the intervention and 4 days after completion, patients on dialysis or with GFR< 30 ml/min/1.73 m2, severe neutropenia, thrombocytopenia or COVID-vaccinated patients.
The primary outcome was a composite of hospitalization for any cause ≥24 hours and death within 29 days. In the treatment group, 6.8% were hospitalized or died through day 29 vs 9.7% in the placebo group with treatment difference of 2.9% (95% CI, -5.9 to -0.1). The number needed to treat was 34 patients. This was lower than the treatment difference in the interim analysis (7.3% vs 14.1%). Secondary analyses (in the supplement) showed that the molnupiravir group had improvement in WHO Clinical Progression Scale by day 5, lower likelihood of symptom progression, and larger reduction in viral load at days 3 and 5. There was no statistically significant difference in adverse events.
The big picture: Molnupiravir has been shown to have lower efficacy than other agents that have been studied, such as Paxlovid, and the FDA has approved this as a therapeutic option when other FDA-authorized treatments are not available (see NIH guidelines here).
In addition, molnupiravir is believed to be a teratogen (see FDA Fact Sheet), and patients should use a reliable form of contraception (females: during treatment and for 4 days after; males: for at least 3 months after treatment), which raises some concern for compliance.
Molnupiravir for Oral Treatment of Covid-19 in Nonhospitalized Patients. N Engl J Med 2022 Feb 10; 386(6): 509-520. Doi: 10.1056/NEJMoa2116044. Epub 2021 Dec 16.