Molnupiravir, an Oral Antiviral Treatment for COVID-19
MD William Fischer, MD Joseph J Eron Jr, MD Wayne Holman, MD Myron S Cohen, Lei Fang, Laura J Szewczyk, PhD Timothy P Sheahan, Ralph Baric, MS Katie R Mollan, MBBS MPH Cameron R Wolfe, MD Elizabeth R Duke, MD Masoud M Azizad, Katyna Borroto-Esoda, MD David A Wohl, BSc Amy James Loftis, BSc Paul Alabanza, Felicia Lipansky, MD, MPH Wendy P Painter
doi:10.1101/2021.06.17.21258639
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 All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
Change from Baseline in SARS-CoV-2 Viral Load The decrease in viral RNA from baseline to Days 3 to 28 was greater for the 800 mg molnupiravir group than any other group (Table 2 and Figure 2c ). For participants administered 400 or 800 mg molnupiravir, the least squares mean viral load change from baseline was significantly greater on Day 5 when compared to placebo, with differences in least squares means of -0.434 and -0.547 log 10 copies/mL (p = 0.03 and 0.006), respectively. Additionally, for participants administered 800 mg molnupiravir, the least squares mean viral load change from baseline was also significantly greater on Day 7 compared to placebo, with a least squares mean difference of -0.534 log 10 copies/mL (p = 0.006). The reduction in viral load from baseline to Day 5 between 800 mg molnupiravir and placebo remained significant during sensitivity analyses of participants who were negative for antibodies at baseline (least squares mean difference of -0.613 log 10 copies/mL; p = 0.002; Supplementary Table 6 ) and when compared to concurrent placebo (least squares mean difference of -0.376 log 10 copies/mL; p = 0.045; Supplementary Table 8 ).
SARS-CoV-2 Antibody Detection Participants were tested for SARS-CoV-2-specific immunoglobulin (Ig) A, IgM, and IgG at baseline and on Days 7 and 28. The proportions of participants with any antibody to SARS-CoV-2 at baseline varied between the groups, with 15.0%, 30.0%, 35.3%, and 18.2% in the 200, 400, 800 mg..
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"abstract": "<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>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 (<jats:ext-link xmlns:xlink=\"http://www.w3.org/1999/xlink\" ext-link-type=\"uri\" xlink:href=\"http://ClinicalTrials.gov\">ClinicalTrials.gov</jats:ext-link><jats:ext-link xmlns:xlink=\"http://www.w3.org/1999/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT04405570\">NCT04405570</jats:ext-link>).</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>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.</jats:p></jats:sec>",
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