Author:
Fischer William,Eron Joseph J.,Holman Wayne,Cohen Myron S.,Fang Lei,Szewczyk Laura J.,Sheahan Timothy P,Baric Ralph,Mollan Katie R.,Wolfe Cameron R.,Duke Elizabeth R.,Azizad Masoud M.,Borroto-Esoda Katyna,Wohl David A.,Loftis Amy James,Alabanza Paul,Lipansky Felicia,Painter Wendy P.
Abstract
AbstractBackgroundEasily 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.govNCT04405570).MethodsEligible 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.ResultsAmong 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.ConclusionsMolnupiravir 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.
Publisher
Cold Spring Harbor Laboratory
Reference24 articles.
1. World Health Organisation. Weekly epidemiological update on COVID-19 - 25 May 2021 [Internet]. Coronavirus Dis. COVID-19 Pandemic. [cited 2021 May 26];Available from: https://www.who.int/publications/m/item/weekly-epidemiological-update-on-covid-19---25-may-2021
2. SARS-CoV-2 Neutralizing Antibody LY-CoV555 in Outpatients with Covid-19;N Engl J Med,2021
3. Author Correction: Virological assessment of hospitalized patients with COVID-2019;Nature,2020
4. Duration and key determinants of infectious virus shedding in hospitalized patients with coronavirus disease-2019 (COVID-19)
5. Viral dynamics in mild and severe cases of COVID-19;Lancet Infect Dis,2020