Background
New treatments are needed to reduce the risk of progression of coronavirus disease 2019 (Covid-19). Molnupiravir is a small molecule oral antiviral prodrug that is active against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
Methods
We conducted a phase 3, double-blind, randomized, placebo-controlled trial to evaluate the efficacy and safety of molnupiravir treatment initiated within 5 days of the onset of signs or symptoms in non-hospitalized, non-vaccinated adults. laboratory confirmed for mild to moderate Covid-19 and at least one risk factor for severe Covid-19 disease.
Participants in the trial were randomly assigned to receive 800 mg of molnupiravir or placebo twice daily for 5 days.
The primary efficacy endpoint was the incidence of hospitalization or death at day 29; the incidence of adverse events was the primary safety end point.
A planned interim analysis was performed when 50% of the 1550 participants (target enrollment) had been followed up to day 29.
Results
A total of 1433 participants were randomized; 716 were assigned to receive molnupiravir and 717 to receive placebo. With the exception of an imbalance in sex, baseline characteristics were similar in the two groups.
The superiority of molnupiravir was demonstrated in the interim analysis; the risk of all-cause hospitalization or death through day 29 was lower with molnupiravir (28 of 385 participants [7.3%]) than with placebo (53 of 377 [14.1%]) (difference, −6.8 percentage points; 95% confidence interval). [CI], -11.3 to -2.4; P = 0.001).
In the analysis of all participants who had been randomized, the percentage of participants who were hospitalized or died through day 29 was lower in the molnupiravir group than in the placebo group (6.8% [48 of 709] vs. 9.7% [68 of 699]; difference, −3.0 percentage points; 95% CI, −5.9 to −0.1).
The results of the subgroup analyzes were largely consistent with these overall results; In some subgroups, such as patients with evidence of prior SARS-CoV-2 infection, those with a low baseline viral load, and those with diabetes, the point estimate of the difference favored placebo.
One death was reported in the molnupiravir group and 9 in the placebo group through day 29. Adverse events were reported in 216 of 710 participants (30.4%) in the molnupiravir group and 231 of 701 (33.0% ) in the placebo group.
Conclusions Early treatment with molnupiravir reduced the risk of hospitalization or death in unvaccinated and at-risk adults with Covid-19. |
(Funded by Merck Sharp and Dohme; MOVe-OUT ClinicalTrials.gov number, NCT04575597. opens in new tab.)
