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
medRxiv. 2021 Jun 17:2021.06.17.21258639. doi: 10.1101/2021.06.17.21258639.
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 ).
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.
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.
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.
迫切需要易于分发的口服抗病毒药物来治疗2019冠状病毒病（COVID-19），预防疾病进展为重症，并阻断严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的传播。我们报告了一项2a期试验的结果，该试验评估了莫努匹韦治疗COVID-19的安全性、耐受性和抗病毒疗效（ClinicalTrials.gov NCT04405570）。
符合条件的参与者包括确诊感染SARS-CoV-2且症状出现时间在7天内的门诊患者。参与者按1:1随机分为200mg莫努匹韦组或安慰剂组，或按3:1随机分为莫努匹韦（400或800mg）组或安慰剂组，每日两次，持续5天。抗病毒活性通过逆转录聚合酶链反应检测病毒RNA达到不可检测水平的时间以及从鼻咽拭子中消除传染性病毒分离物的时间来评估。
在202名接受治疗的参与者中，第3天接受800mg莫努匹韦的参与者病毒分离率（1.9%）显著低于接受安慰剂的参与者（16.7%）（p = 0.02）。第5天，接受400或800mg莫努匹韦的参与者均未分离出病毒，而接受安慰剂的参与者中这一比例为11.1%（p = 0.03）。与安慰剂相比，接受800mg莫努匹韦的参与者病毒RNA清除时间缩短，总体上实现清除的比例更高（p = 0.01）。莫努匹韦总体耐受性良好，所有组的不良事件数量相似。
莫努匹韦是首个口服直接作用抗病毒药物，在减少鼻咽部SARS-CoV-2传染性病毒和病毒RNA方面显示出高效性，且具有良好的安全性和耐受性。
