Antiviral Efficacy and Safety of Molnupiravir Against Omicron Variant Infection: A Randomized Controlled Clinical Trial
Frontiers in Pharmacology, doi:10.3389/fphar.2022.939573
Background: The rapid worldwide spread of the Omicron variant of SARS-CoV-2 has unleashed a new wave of COVID-19 outbreaks. The efficacy of molnupiravir, an approved drug, is still unknown in patients infected with the Omicron variant. Objective: Evaluated the antiviral efficacy and safety of molnupiravir in patients infected with SARS-CoV-2 Omicron variant, with symptom duration within 5 days. Methods: We conducted a randomized, controlled trial involving patients with mild or moderate COVID-19. Patients were randomized to orally receive molnupiravir (800 mg) plus basic treatment or only basic treatment for 5 days (BID). The antiviral efficacy of the drug was evaluated using reverse transcriptase polymerase chain reaction. Results: Results showed that the time of viral RNA clearance (primary endpoint) was significantly decreased in the molnupiravir group (median, 9 days) compared to the control group (median, 10 days) (Log-Rank p = 0.0092). Of patients receiving molnupiravir, 18.42% achieved viral RNA clearance on day 5 of treatment, compared to the control group (0%) (p = 0.0092). On day 7, 40.79%, and 6.45% of patients in the molnupiravir and control groups, respectively, achieved viral RNA clearance (p = 0.0004). In addition, molnupiravir has a good safety profile, and no serious adverse events were reported.
Conclusion: Molnupiravir significantly accelerated the SARS-CoV-2 Omicron RNA clearance in patients with COVID-19.
ETHICS STATEMENT The studies involving human participants were reviewed and approved by the Medical Ethics Committee of the Third People's Hospital of Shenzhen (No. 2022-034-02) . The patients/ participants provided their written informed consent to participate in this study.
SUPPLEMENTARY MATERIAL The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fphar.2022.939573/ full#supplementary-material Conflict of Interest: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Publisher's Note: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.
Arora, Zhang, Rocha, Sidarovich, Kempf et al., Comparable Neutralisation Evasion of SARS-CoV-2 Omicron Subvariants BA.1, BA.2, and BA.3, Lancet. Infect. Dis, doi:10.1016/s1473-3099(22)00224-9
Bernal, Gomes Da Silva, Musungaie, Kovalchuk, Gonzalez et al., Molnupiravir for Oral Treatment of Covid-19 in Nonhospitalized Patients, N. Engl. J. Med, doi:10.1056/NEJMoa2116044
Chen, Wang, Gilby, Wei, Omicron Variant (B.1.1.529): Infectivity, Vaccine Breakthrough, and Antibody Resistance, J. Chem. Inf. Model, doi:10.1021/acs.jcim.1c01451
Cheng, Ip, Chu, Tam, Chan et al., Rapid Spread of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Omicron Subvariant BA.2 in a Single-Source Community Outbreak, Clin. Infect. Dis, doi:10.1093/cid/ciac203
Fischer, Eron, Jr, Holman, Cohen et al., A Phase 2a Clinical Trial of Molnupiravir in Patients with COVID-19 Shows Accelerated SARS-CoV-2 RNA Clearance and Elimination of Infectious Virus, doi:10.1126/scitranslmed.abl7430
He, Hong, Pan, Lu, Wei, SARS-CoV-2 Omicron Variant: Characteristics and Prevention, MedComm, doi:10.1002/mco2.110
Merck, Merck and Ridgeback's Molnupiravir, an Oral COVID-19 Antiviral Medicine
Rosenke, Okumura, Lewis, Feldmann, Meade-White et al., Molnupiravir Inhibits SARS-CoV-2 Variants Including Omicron in the Hamster Model, JCI Insight, doi:10.1172/jci.insight.160108
Saxena, Kumar, Ansari, Paweska, Maurya et al., Characterization of the Novel SARS-CoV-2 Omicron (B.1.1.529) Variant of Concern and its Global Perspective, J. Med. Virol, doi:10.1002/jmv.27524
Takashita, Kinoshita, Yamayoshi, Sakai-Tagawa, Fujisaki et al., Efficacy of Antibodies and Antiviral Drugs against Covid-19 Omicron Variant, N. Engl. J. Med, doi:10.1056/NEJMc2119407
Uraki, Kiso, Iida, Imai, Takashita et al., Characterization and Antiviral Susceptibility of SARS-CoV-2 Omicron/BA.2, Nature, doi:10.1038/s41586-022-04856-1