Early treatment with molnupiravir, an oral, small-molecule antiviral prodrug, reduced the risk of hospitalisation or death in at-risk, unvaccinated adults with coronavirus disease 2019 (COVID-19), according to a study published in The New England Journal of Medicine.
“These data from the MOVe-OUT Phase III trial in nonhospitalised at-risk adults with COVID-19 indicate that molnupiravir, initiated within 5 days after the onset of symptoms, reduces the risk of hospitalisation for any cause or death through day 29,” wrote Angélica Jayk Bernal, MD, Oncomedica SA, Monteria, Colombia, and colleagues, noting that “the risk of hospitalisation or death at day 29 was 6.8 percentage points lower with molnupiravir than with placebo at the interim analysis and 3.0 percentage points lower in the all-randomised analysis, an improvement in an outcome that is potentially meaningful for patients, health care systems, and public health.”
A total of 1,433 nonhospitalised, unvaccinated adults with mild-to-moderate, laboratory-confirmed COVID-19 and at least one risk factor for severe COVID-19 illness were randomly assigned to receive 800 mg of molnupiravir (n = 716) or placebo (n = 717) twice daily for 5 days. With the exception of an imbalance in sex, baseline characteristics were similar in the two groups. Overall, 47.7% of the participants had an onset of signs or symptoms 3 days or less before randomisation, and 44.5% of the participants had moderate COVID-19. The most common risk factors were obesity (73.7%), age over 60 years (17.2%), and diabetes mellitus (15.9%). Almost all the participants (98.3%; 709 in the molnupiravir group and 699 in the placebo group) were included in the modified intention-to-treat population.
Overall, the superiority of molnupiravir was demonstrated at the interim analysis, whereby the risk of hospitalisation for any cause or death through day 29 was lower among participants treated with molnupiravir compared with those treated with placebo (7.3% [28 of 385] vs 14.1% [53 of 377]; 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 undergone randomisation, the proportion of participants who were hospitalised 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% confidence interval, −5.9 to −0.1).
The results of a post hoc analysis adjusted for participant sex were consistent with those of the primary analysis, with a risk of hospitalisation or death through day 29 that was lower by 2.8 percentage points (95% CI, −5.7 to 0.1) with molnupiravir over placebo. The results of a time-to-event analysis were also consistent with the primary results, with the rate of hospitalisation or death through day 29 being approximately 31% lower with molnupiravir than with placebo (hazard ratio, 0.69; 95% CI, 0.48 to 1.01).
Safety wise, the percentage of participants with at least one adverse event was similar in the two groups (30.4% in the molnupiravir group and 33.0% in the placebo group), as was the percentage of participants with adverse events considered by the investigators to be related to the trial regimen (8.0% vs 8.4%).
“In this trial, oral molnupiravir was found to be effective for the treatment of COVID-19, without evident safety concerns, when initiated within 5 days after the onset of signs or symptoms in this population of nonhospitalised, unvaccinated adults who were at risk for progression to severe disease,” the authors noted, adding that “the trial population was representative of real-world patients with one or more well-established risk factors for severe illness due to COVID-19.”
Nonetheless, the authors pointed out that “since pregnancy was an exclusion criterion in this trial, the potential impact of molnupiravir on fetal development is unknown.”
Further, the authors acknowledged that “only patients not vaccinated against COVID-19 were eligible for [the] trial, a choice made both to focus on those most likely to need antiviral treatment and to facilitate more rapid evaluation of the therapeutic efficacy of molnupiravir. The potential benefit of molnupiravir for the treatment of COVID-19 vaccine breakthrough infections was thus not evaluated.”