Molnupiravir, an Oral Antiviral Treatment for COVID-19

 William A Fischer II, Joseph J Eron Jr., Wayne Holman, Myron S Cohen, Lei Fang, Laura J Szewczyk, Timothy P Sheahan, Ralph S Baric, Katie R Mollan, Cameron R Wolfe, Elizabeth R Duke, Masoud M Azizad, Katyna BorrotoiEsoda, David A Wohl, Amy James Loftis, Paul Alabanza, Felicia Lipansky, Wendy P Painter

doi: https://doi.org/10.1101/2021.06.17.21258639

This article is a preprint and has not been certified by peer review [what does this mean?]. It reports new medical research that has yet to be evaluated and so should not be used to guide clinical practice.

PDF: https://www.medrxiv.org/content/10.1101/2021.06.17.21258639v1.full.pdf

Abstract

Background: Easily distributed oral antivirals are urgently needed to treat coronavirus disease-2019 (COVID-19), prevent progression to severe illness, and block transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We report the results of a Phase 2a trial evaluating the safety, tolerability, and antiviral efficacy of molnupiravir in the treatment of COVID-19 (ClinicalTrials.gov NCT04405570). Methods: Eligible participants included outpatients with confirmed SARS-CoV-2 infection and symptom onset within 7 days. Participants were randomized 1:1 to 200 mg molnupiravir or placebo, or 3:1 to molnupiravir (400 or 800 mg) or placebo, twice daily for 5 days. Antiviral activity was assessed as time to undetectable levels of viral RNA by reverse transcriptase polymerase chain reaction and time to elimination of infectious virus isolation from nasopharyngeal swabs. Results: Among 202 treated participants, virus isolation was significantly lower in participants receiving 800 mg molnupiravir (1.9%) versus placebo (16.7%) at Day 3 (p = 0.02). At Day 5, virus was not isolated from any participants receiving 400 or 800 mg molnupiravir, versus 11.1% of those receiving placebo (p = 0.03). Time to viral RNA clearance was decreased and a greater proportion overall achieved clearance in participants administered 800 mg molnupiravir versus placebo (p = 0.01). Molnupiravir was generally well tolerated, with similar numbers of adverse events across all groups. Conclusions: Molnupiravir is the first oral, direct acting antiviral shown to be highly effective at reducing nasopharyngeal SARS-CoV-2 infectious virus and viral RNA and has a favorable safety and tolerability profile.

Competing Interest Statement

All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare the following: PA, FL, WP, LS, and WH were employed by Ridgeback Biotherapeutics in direct support of the work reported in this manuscript. MA, WF, KM, and RB were contracted by Ridgeback Biotherapeutics in direct support of the work reported in this manuscript. JE, WP, TS, DW, CW, and WF are independent contractors who were topically related to this study within the past 36 months. MC was employed by UNC at Chapel Hill and received a grant from the National Institute of Health in direct support of the work presented in this manuscript. KM has stocks or stock options in ICON Plc. WP and WH received royalties from patents, trademarks, copyrights or other intellectual property. WH has stock or stock options and is a fiduciary offer or member of another board. LF, KB-E, AJL and ED declared no conflicts of interest. The initial draft of this manuscript was prepared by Mark Stead of Covance Clinical Research Unit Limited, UK.

Clinical Trial

NCT04405570

Funding Statement

Molnupiravir was invented at Drug Innovations at Emory (DRIVE) LLC, a not for profit biotechnology company wholly owned by Emory University, and with partial funding support from the US government. Since licensed by Ridgeback Biotherapeutics, all funds used for the development of molnupiravir by Ridgeback Biotherapeutics have been provided by Wayne and Wendy Holman and Merck.

https://www.medrxiv.org/content/10.1101/2021.06.17.21258639v1