Three new studies to be presented at the upcoming European Congress of Clinical Microbiology & Infectious Diseases (ECCMID) conference at the end of the month (Lisbon, 23-26 April) demonstrate benefits of the antiviral molnupiravir against COVID-19 infections, including evidence that Merck’s pill reduces symptoms of the SARS-CoV-2 virus by the third day of administration.
Cidrap (US Centre for Infectious Disease Research & Policy) reports that all three studies are based on results seen in the MOVe-OUT study, which was conducted throughout 2021 to determine the drug’s efficacy against COVID-19 infections.
In the first study, participants were randomised and given molnupiravir or placebo within five days of symptom onset. Participants kept a daily record of COVID-19 symptoms for a month. Those who took molnupiravir saw significant reduction of symptoms by day three and five, including shortness of breath or difficulty breathing, cough, fatigue, loss of smell, and loss of taste.
In a second study, the antiviral pill was able to clear active SARS-CoV-2 virus equally well in immunocompromised patients, as well as those who were deemed immune-competent. Of the 1,433 participants in MOVe-OUT, 57 (4%) were identified as immune-compromised. Of those participants, only two of 25 (8%) given molnupiravir were hospitalised or died from COVID-19, compared with eight of 32 (25%) of immune-compromised patients given a placebo.
In a final study, PCR testing was used to determine viral loads from nasopharyngeal swabs collected on days 1 (baseline), 3, 5 (end-of- treatment visit), 10, 15, and 29. By the third day of treatment, among patients with infectious virus at baseline, infectious SARS-CoV-2 was detected in none of the 92 patients who received molnupiravir, compared with 20 (20.8%) of 96 patients who received a placebo. By day 5, virus was detected in 0.0% in the molnupiravir arm of the study compared with 2.2% in the placebo arm.
“This study provides additional evidence that molnupiravir helps those infected clear SARS-CoV-2 faster than placebo, and supports MOVe- OUT's primary finding that molnupiravir can lower the risk of progression to serious illness in this high-risk cohort,” said Julie Strizki, PhD, a researcher at Merck.
MOVe-OUT Study details
Molnupiravir for Oral Treatment of Covid-19 in Nonhospitalized Patients
Angélica Jayk Bernal, Monica M. Gomes da Silva, Dany B. Musungaie, Evgeniy Kovalchuk, Antonio Gonzalez, Virginia Delos Reyes, Alejandro Martín-Quirós, Yoseph Caraco, Angela Williams-Diaz, Michelle L. Brown, Jiejun Du, Alison Pedley, et al., for the MOVe-OUT Study Group
Published in The New England Journal of Medicine (NEJM) on 10 February 2022
Abstract
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, randomised, 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 non-hospitalised, 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 hospitalisation 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 enrolment) had been followed through day 29.
Results
A total of 1433 participants underwent randomisation; 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 hospitalisation 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 [CI], −11.3 to −2.4; P=0.001). In the analysis of all participants who had undergone randomisation, the percentage 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% CI, −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 hospitalisation or death in at-risk, unvaccinated adults with COVID-19.
Cidrap article – Molnupiravir reduces COVID-19 symptoms, virus by day 3, data show (Open access)
NEJM article – Molnupiravir for Oral Treatment of Covid-19 in Nonhospitalized Patients (Open access)
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