Randomized Trial of Molnupiravir or Placebo in Patients Hospitalized with Covid-19
et al., NEJM Evidence, doi:10.1056/EVIDoa2100044, NCT04575584 (history)
, Randomized Trial of Molnupiravir or Placebo in Patients Hospitalized with Covid-19, NEJM Evidence, doi:10.1056/EVIDoa2100044, NCT04575584
RCT 304 hospitalized patients, 218 treated with molnupiravir, showing no significant differences. MOVe-IN MK-4482-001. NCT04575584 (history).Concerns have been raised that the mutagenic mechanism of action may create dangerous variants or cause cancer [Hadj Hassine, Swanstrom]. See [Fountain-Jones, Sanderson, twitter.com] for analysis of variants potentially created by molnupiravir.
1.
Fountain-Jones et al., medRxiv, doi:10.1101/2022.12.21.22283811,
Antiviral treatments lead to the rapid accrual of hundreds of SARS-CoV-2 mutations in immunocompromised patients,
https://www.medrxiv.org/content/10.1101/2022.12.21.22283811.
2.
Hadj Hassine et al., Viruses, doi:10.3390/v14040841,
Lethal Mutagenesis of RNA Viruses and Approved Drugs with Antiviral Mutagenic Activity,
https://www.mdpi.com/1999-4915/14/4/841.
3.
Sanderson et al., medRxiv, doi:10.1101/2023.01.26.23284998,
Identification of a molnupiravir-associated mutational signature in SARS-CoV-2 sequencing databases,
https://www.medrxiv.org/content/10.1101/2023.01.26.23284998.
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risk of death, 281.9% higher, RR 3.82, p = 0.31, treatment 11 of 216 (5.1%), control 1 of 75 (1.3%), combined, excluding imputed deaths.
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risk of death, 216.9% higher, RR 3.17, p = 0.36, treatment 3 of 71 (4.2%), control 1 of 75 (1.3%), 800mg, excluding imputed death.
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risk of death, 316.7% higher, RR 4.17, p = 0.20, treatment 4 of 72 (5.6%), control 1 of 75 (1.3%), 400mg, excluding imputed death.
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risk of death, 311.0% higher, RR 4.11, p = 0.21, treatment 4 of 73 (5.5%), control 1 of 75 (1.3%), 200mg.
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risk of no recovery, 1.0% lower, RR 0.99, p = 0.96, treatment 72, control 75, inverted to make RR<1 favor treatment, 800mg.
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risk of no recovery, 11.5% lower, RR 0.88, p = 0.53, treatment 73, control 75, inverted to make RR<1 favor treatment, 400mg.
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risk of no recovery, 1.0% higher, RR 1.01, p = 0.96, treatment 73, control 75, inverted to make RR<1 favor treatment, 200mg.
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recovery time, no change, relative time 1.00, treatment 72, control 75, 800mg.
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recovery time, no change, relative time 1.00, treatment 73, control 75, 400mg.
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recovery time, no change, relative time 1.00, treatment 73, control 75, 200mg.
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risk of no viral clearance, 11.8% lower, RR 0.88, p = 0.57, treatment 26 of 52 (50.0%), control 34 of 60 (56.7%), NNT 15, 800mg, Table S16, day 15 mid-recovery.
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risk of no viral clearance, 2.4% higher, RR 1.02, p = 1.00, treatment 29 of 50 (58.0%), control 34 of 60 (56.7%), 400mg, Table S16, day 15 mid-recovery.
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risk of no viral clearance, 20.6% lower, RR 0.79, p = 0.27, treatment 27 of 60 (45.0%), control 34 of 60 (56.7%), NNT 8.6, 200mg, Table S16, day 15 mid-recovery.
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risk of no viral clearance, 8.3% lower, RR 0.92, p = 1.00, treatment 9 of 53 (17.0%), control 10 of 54 (18.5%), NNT 65, 800mg, Table S16, day 29.
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risk of no viral clearance, 48.2% higher, RR 1.48, p = 0.35, treatment 14 of 51 (27.5%), control 10 of 54 (18.5%), 400mg, Table S16, day 29.
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risk of no viral clearance, 21.5% lower, RR 0.79, p = 0.61, treatment 8 of 55 (14.5%), control 10 of 54 (18.5%), NNT 25, 200mg, Table S16, day 29.
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Arribas et al., 16 Dec 2021, Double Blind Randomized Controlled Trial, multiple countries, peer-reviewed, 21 authors, average treatment delay 7.1 days, trial NCT04575584 (history).
Abstract: Published December 16, 2021
DOI: 10.1056/EVIDoa2100044
ORIGINAL ARTICLE
Randomized Trial of Molnupiravir or Placebo in
Patients Hospitalized with Covid-19
Jose R. Arribas, M.D.1, Sanjay Bhagani, M.D.2, Suzana M. Lobo, M.D., Ph.D.3, Ilsiyar Khaertynova, M.D.4,
Lourdes Mateu, M.D., Ph.D.5, Roman Fishchuk, M.D.6, William Y. Park, M.D.7, Khetam Hussein, M.D.8, Sei Won Kim, M.D.9,
Jade Ghosn, M.D.10,11, Michelle L. Brown, B.S.12, Ying Zhang, Ph.D.12, Wei Gao, Ph.D.12, Christopher Assaid, Ph.D.12,
Jay A. Grobler, Ph.D.12, Julie Strizki, Ph.D.12, Mary Vesnesky, B.A.12, Amanda Paschke, M.D.12, Joan R. Butterton, M.D.12,
Carisa De Anda, Pharm.D.12, on behalf of the MOVe-IN study group
Abstract
BACKGROUND Molnupiravir is an oral prodrug of b-D-N4-hydroxycytidine, active against
SARS-CoV-2 in vitro and in animal models. We report data from the phase 2 component
of MOVe-IN, a clinical trial evaluating molnupiravir in patients hospitalized with
Covid-19.
METHODS We conducted a randomized, placebo-controlled, double-blind phase 2/3
trial in patients 18 years old and older requiring in-hospital treatment for laboratoryconfirmed Covid-19 with symptom onset 10 or fewer days before randomization. Participants were randomly assigned to placebo or molnupiravir 200 mg, 400 mg, or 800 mg
(1:1:1:1 ratio), twice daily for 5 days. Primary end points were safety and sustained recovery (participant alive and either not hospitalized or medically ready for discharge)
through day 29.
RESULTS Of 304 randomly assigned participants, 218 received at least one dose of molnupiravir and 75 of placebo. At baseline, 74.0% had at least one risk factor for severe
Covid-19. Adverse events were reported in 121 of 218 (55.5%) molnupiravir-treated and
46 of 75 (61.3%) placebo-treated participants, with no apparent dose effect on adverse
event rates and no evidence of hematologic toxicity based on prespecified adverse
events. Of 16 confirmed deaths, most were in participants with severe Covid-19 (75.0%),
with underlying comorbidities (87.5%), older than 60 years of age (81.3%), and/or symptom duration longer than 5 days (75.0%) at randomization. Median time to sustained
recovery was 9 days in all groups, with similar day 29 recovery rates ranging from 81.5%
to 85.2%.
CONCLUSIONS In this phase 2 trial of patients hospitalized with Covid-19, a 5-day
course of molnupiravir up to 800 mg twice daily was not associated with dose-limiting
For personal use only. No other uses without permission. Copyright © 2021 Massachusetts Medical Society.
The author affiliations are listed
at the end of the article.
Dr. De Anda can be contacted at
carisa.de.anda@merck.com or at
Merck & Co. Inc., 309 N
Sumneytown Pike, North Wales,
PA 19454.
side effects or adverse events, but did not demonstrate
clinical benefit. (Funded by Merck Sharp & Dohme;
ClinicalTrials.gov NCT04575584.)
Late treatment
is less effective
is less effective
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