Optimus announces Interim Clinical Results from Phase III Clinical Trials of Molnupiravir conducted in India
, Press Release, Oct 2021
RCT 1,202 patients showing improved viral clearance, but no significant differences in clinical outcomes. Only interim results were reported by the manufacturer, the final results are from1. Some results are provided only as percentages without confirming if data was available for all patients - we assume all patients had data available.
Potential risks of molnupiravir include the creation of dangerous variants, and mutagenicity, carcinogenicity, teratogenicity, and embryotoxicity2-16. Multiple analyses have identified variants potentially created by molnupiravir17-21. Studies show significantly increased risk of acute kidney injury22 and neurological symptoms22.
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risk of hospitalization, 75.2% lower, RR 0.25, p = 0.22, treatment 1 of 603 (0.2%), control 4 of 599 (0.7%), NNT 199, day 14.
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no 2-point ordinal scale improvement, 15.5% higher, RR 1.15, p = 0.03, treatment 286 of 603 (47.4%), control 246 of 599 (41.1%), day 28.
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no 2-point ordinal scale improvement, 14.9% higher, RR 1.15, p = 0.02, treatment 303 of 603 (50.2%), control 262 of 599 (43.7%), day 14.
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no 2-point ordinal scale improvement, 8.7% lower, RR 0.91, p = 0.09, treatment 308 of 603 (51.1%), control 335 of 599 (55.9%), NNT 21, day 10.
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no 2-point ordinal scale improvement, 4.0% lower, RR 0.96, p = 0.27, treatment 431 of 603 (71.5%), control 446 of 599 (74.5%), NNT 34, day 5.
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no 1-point ordinal scale improvement, 27.7% higher, RR 1.28, p = 0.80, treatment 9 of 603 (1.5%), control 7 of 599 (1.2%), day 28.
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no 1-point ordinal scale improvement, 32.4% higher, RR 1.32, p = 0.66, treatment 12 of 603 (2.0%), control 9 of 599 (1.5%), day 14.
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no 1-point ordinal scale improvement, 87.8% lower, RR 0.12, p < 0.001, treatment 13 of 603 (2.2%), control 106 of 599 (17.7%), NNT 6.4, day 10.
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no 1-point ordinal scale improvement, 46.1% lower, RR 0.54, p < 0.001, treatment 127 of 603 (21.1%), control 234 of 599 (39.1%), NNT 5.6, day 5.
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risk of no viral clearance, 40.6% lower, RR 0.59, p < 0.001, treatment 174 of 603 (28.9%), control 291 of 599 (48.6%), NNT 5.1, mid-recovery, day 5.
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risk of no viral clearance, 0.7% lower, RR 0.99, p = 1.00, treatment 7 of 603 (1.2%), control 7 of 599 (1.2%), NNT 12900, day 14.
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risk of no viral clearance, 86.0% lower, RR 0.14, p < 0.001, treatment 13 of 603 (2.2%), control 92 of 599 (15.4%), NNT 7.6, day 10.
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| Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates |
2.
Swanstrom et al., Lethal mutagenesis as an antiviral strategy, Science, doi:10.1126/science.abn0048.
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Hadj Hassine et al., Lethal Mutagenesis of RNA Viruses and Approved Drugs with Antiviral Mutagenic Activity, Viruses, doi:10.3390/v14040841.
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Shum, C., An investigational study into the drug-associated mutational signature in SARS-CoV-2 viruses, The University of Hong Kong, PhD Thesis, hub.hku.hk/handle/10722/344396.
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Waters et al., Human genetic risk of treatment with antiviral nucleoside analog drugs that induce lethal mutagenesis: the special case of molnupiravir, Environmental and Molecular Mutagenesis, doi:10.1002/em.22471.
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Huntsman, M., An assessment of the reproductive toxicity of the anti-COVID-19 drug molnupiravir using stem cell-based embryo models, Master's Thesis, scholarspace.manoa.hawaii.edu/items/cd11342c-b4dc-44c0-8b44-ce6e3369c40b.
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Huntsman (B) et al., Detection of developmental toxicity of the anti-COVID-19 drug molnupiravir using gastruloid-based in vitro assays, Toxicological Sciences, doi:10.1093/toxsci/kfaf093.
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Zibat et al., N4-hydroxycytidine, the active compound of Molnupiravir, promotes SARS-CoV-2 mutagenesis and escape from a neutralizing nanobody, iScience, doi:10.1016/j.isci.2023.107786.
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Shiraki et al., Convenient screening of the reproductive toxicity of favipiravir and antiviral drugs in Caenorhabditis elegans, Heliyon, doi:10.1016/j.heliyon.2024.e35331.
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Gruber et al., Molnupiravir increases SARS‐CoV‐2 genome diversity and complexity: A case‐control cohort study, Journal of Medical Virology, doi:10.1002/jmv.29642.
11.
Marikawa et al., An active metabolite of the anti-COVID-19 drug molnupiravir impairs mouse preimplantation embryos at clinically relevant concentrations, Reproductive Toxicology, doi:10.1016/j.reprotox.2023.108475.
12.
Rahman, M., Elucidation of the DNA repair mechanisms involved in the repair of DNA damage caused by the Arabinosides and Anti-COVID-19 drugs, tokyo-metro-u.repo.nii.ac.jp/records/2000972.
13.
Zhou et al., β-D-N4-hydroxycytidine Inhibits SARS-CoV-2 Through Lethal Mutagenesis But Is Also Mutagenic To Mammalian Cells, The Journal of Infectious Diseases, doi:10.1093/infdis/jiab247.
14.
Chamod et al., Molnupiravir Metabolite--N4-hydroxycytidine Causes Cytotoxicity and DNA Damage in Mammalian Cells in vitro: N4-hydroxycytidine Induced Cytotoxicity DNA Damage, Asian Medical Journal and Alternative Medicine, 23:3, asianmedjam.com/index.php/amjam/article/view/1448.
15.
Standing et al., Randomized controlled trial of molnupiravir SARS-CoV-2 viral and antibody response in at-risk adult outpatients, Nature Communications, doi:10.1038/s41467-024-45641-0.
16.
Mori et al., Reactive oxygen species-mediated cytotoxic and DNA-damaging mechanism of N4-hydroxycytidine, a metabolite of the COVID-19 therapeutic drug molnupiravir, Free Radical Research, doi:10.1080/10715762.2025.2469738.
17.
Focosi et al., The fitness of molnupiravir-signed SARS-CoV-2 variants: imputation analysis based on prescription counts and GISAID analyses by country, Intervirology, doi:10.1159/000540282.
18.
Sanderson et al., A molnupiravir-associated mutational signature in global SARS-CoV-2 genomes, Nature, doi:10.1038/s41586-023-06649-6.
19.
Fountain-Jones et al., Effect of molnupiravir on SARS-CoV-2 evolution in immunocompromised patients: a retrospective observational study, The Lancet Microbe, doi:10.1016/S2666-5247(23)00393-2.
Optimus et al., 28 Oct 2021, Randomized Controlled Trial, India, preprint, 1 author, licensee.
