Molnupiravir reduces hospitalization in at-risk outpatients with symptomatic COVID-19

Reference

Jayk Bernal A, Gomes da Silva MM, Musungaie DB, et al, for the MOVe-OUT Study Group. Molnupiravir for oral treatment of Covid-19 in nonhospitalized patients. N Engl J Med 2022;386(6):509-520.

Synopsis

Molnupiravir is an oral small molecule with activity against RNA viruses, including SARS-CoV-2. It works by being incorporated into the viral RNA and causing errors that make it unable to replicate. These researchers recruited 1433 adult outpatients with mild to moderate symptomatic COVID-19 infection who had been given their diagnosis no more than 5 days ago. All had at least one of the following risk factors for more severe disease: chronic kidney disease, active cancer, older than 60 years, chronic obstructive pulmonary disease, diabetes mellitus, body mass index 30 or higher, or a serious heart condition. The use of monoclonal antibodies and remdesivir was prohibited through day 29 of the study. Patients who had severe renal disease, were pregnant, or were likely to require imminent hospitalization were excluded, as were patients who had been vaccinated. Recruitment was halted after an interim analysis showed benefit of the drug. The participants were randomized to receive molnupiravir 800 mg twice daily for 5 days or matching placebo. Groups were balanced at the start of the study (with the exception of more women being assigned to molnupiravir), allocation was appropriately concealed, and there were relatively few exclusions (largely because the patient did not receive any placebo or active drug). The patients' median age was 43 years, with approximately one third at least 50 years old, and 55% with mild COVID-19 symptoms. Molnupiravir significantly reduced the likelihood of hospitalization or death at the interim analysis (7.3% vs 14.1%; P = .001; number needed to treat [NNT] = 14) and in the final analysis of all patients in the modified intention-to-treat population (6.8% vs 9.7%; P < .05; NNT = 33). There was 1 death in the molnupiravir group and there were 9 in the placebo group, but the confidence interval around the estimated risk reduction is wide (89% reduction; 95% CI 14% - 99%). Subgroup analyses found a significant benefit if the treatment lasted for more than 3 days from the onset of symptoms compared with 3 days or less. There was no difference between groups in adverse events. There are some long-term safety concerns that molnupiravir may be a mutagen in humans (as is favipiravir, which uses a similar mechanism). These concerns are why molnupiravir is not approved for use in children and not recommended for pregnant adults.