Phase 2/3 Trial of Molnupiravir for Treatment of Covid-19 in Nonhospitalized Adults

Caraco, Yoseph; Crofoot, Gordon; Moncada, Pablo Andrés; Galustyan, A.N.; Musungaie, Dany Badibanga; Payne, Brendan A. I.; Kovalchuk, Evgeniy; González, Antonio; Brown, Michelle; Williams-Diaz, Angela; Gao, Wei; Strizki, Julie; Grobler, Jay A.; Du, Jiejun; Assaid, Christopher; Paschke, Amanda; Butterton, Joan R.; Johnson, Matthew G.; Anda, Carisa De

doi:10.1056/evidoa2100043

Cited by 71 publications

(136 citation statements)

References 19 publications

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“…Secondary end points, including changes in the WHO Clinical Progression Scale and in patient-reported symptoms of Covid-19, also indicated clinical benefits with molnupiravir over placebo. As in previous trials, 7 , 10 , 23 , 24 , 31 no safety concerns with molnupiravir were identified and there was no evidence of a pattern of clinically meaningful abnormalities in laboratory test results. Since pregnancy was an exclusion criterion in this trial, the potential impact of molnupiravir on fetal development is unknown.…”

Section: Discussionsupporting

confidence: 54%

Molnupiravir for Oral Treatment of Covid-19 in Nonhospitalized Patients

Bernal¹,

Silva

Musungaie³

et al. 2022

N Engl J Med

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Background New treatments are needed to reduce the risk of progression of coronavirus disease 2019 (Covid-19). Molnupiravir is an oral, small-molecule 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 treatment with molnupiravir started within 5 days after the onset of signs or symptoms in nonhospitalized, unvaccinated adults with mild-to-moderate, laboratory-confirmed Covid-19 and at least one risk factor for severe Covid-19 illness. Participants in the trial were randomly assigned to receive 800 mg of molnupiravir or placebo twice daily for 5 days. The primary efficacy end point was the incidence 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 1550 participants (target enrollment) had been followed through day 29. Results A total of 1433 participants underwent randomization; 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 at the interim analysis; the risk of hospitalization for any cause 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, −11.3 to −2.4; P=0.001). In the analysis of all participants who had undergone randomization, 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% confidence interval, −5.9 to −0.1). Results of subgroup analyses were largely consistent with these overall results; in some subgroups, such as patients with evidence of previous SARS-CoV-2 infection, those with low baseline viral load, and those with diabetes, the point estimate for the difference favored placebo. One death was reported in the molnupiravir group and 9 were reported 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 at-risk, unvaccinated adults with Covid-19. (Funded by Merck Sharp and Dohme; MOVe-OUT ClinicalTrials.gov number, NCT04575597 .)

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Section: Discussionsupporting

confidence: 54%

Molnupiravir for Oral Treatment of Covid-19 in Nonhospitalized Patients

Bernal¹,

Silva

Musungaie³

et al. 2022

N Engl J Med

Self Cite

1,552

1,583

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“…16 In line with other clinical trials, there were no apparent drug or dose effects on adverse event rates, including no clear impact on mortality. 5,9,10,17,18 As with any new drug, long-term toxicity can only be fully ascertained through ongoing pharmacovigilance.…”

Section: Discussionmentioning

confidence: 99%

“…7 The favorable safety and tolerability profile of molnupiravir seen in preclinical studies and a phase 1 trial provided the needed equipoise for further clinical development. 5,8 The potential of molnupiravir as an antiviral treatment for Covid-19 is being evaluated in two phase 2/3 studies, one in outpatients (MOVe-OUT trial 9,10 ) and the other in hospitalized patients (MOVe-IN trial). In this study, we report safety, efficacy, pharmacokinetic, and virology data from the recently completed phase 2, dose-finding component of MOVe-IN.…”

Section: Introduction Tmentioning

confidence: 99%

Randomized Trial of Molnupiravir or Placebo in Patients Hospitalized with Covid-19

et al. 2022

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Molnupiravir is an oral agent a metabolite of which has activity against SARS-CoV-2. In a controlled trial in adults hospitalized for Covid-19 who had symptoms for 10 days or less prior to randomization, patients received placebo (n=75) or varying doses of molnupiravir (n=218) administered twice-daily for 5 days. There was no impact of treatment on death. Median time to sustained recovery was 9 days in all groups, with day 29 recovery rates ranging from 81.5%-85.2%. There were no dose-limiting side effects or adverse events.

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“…Molnupiravir is less beneficial when administered late in the disease course — namely, after patients have had symptoms for more than 3 to 5 days or after they are hospitalized, as shown in reports of two phase 2 trials of molnupiravir. 8 , 9 Second, the safety database is small and will require careful monitoring for the emergence of side effects. Third, potential mutagenic toxicity has been a concern, since the drug is mutagenic in Chinese hamster ovary cells.…”

mentioning

confidence: 99%

Molnupiravir — A Step toward Orally Bioavailable Therapies for Covid-19

Whitley

2022

N Engl J Med

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Phase 2/3 Trial of Molnupiravir for Treatment of Covid-19 in Nonhospitalized Adults

Cited by 71 publications

References 19 publications

Molnupiravir for Oral Treatment of Covid-19 in Nonhospitalized Patients

Molnupiravir for Oral Treatment of Covid-19 in Nonhospitalized Patients

Randomized Trial of Molnupiravir or Placebo in Patients Hospitalized with Covid-19

Molnupiravir — A Step toward Orally Bioavailable Therapies for Covid-19

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