Efficacy and safety of molnupiravir in adult outpatients with COVID-19

Background: One of the basic principles for the treatment of COVID-19 patients is the early initiation of etiotropic therapy. The evidence base for assessment of the efficacy and safety of antivirals for COVID-19 continues to expand with new clinical trials. One of the promising etiotropic medications is molnupiravir. Aim: To evaluate the efficacy and safety of molnupiravir (Esperavir) in outpatients with COVID-19. Materials and methods: This randomized comparative open-label clinical study was conducted from December 1, 2021 to March 11, 2022 in 12 research centers in the Russian Federation. The study involved 240 outpatients with mild and moderate COVID-19. The mean age of patients was 43.5 years; 70,0% (168/240) of the patients had comorbidities, mainly obesity grade II and arterial hypertension. The outpatients were treated with molnupiravir (Esperavir, PROMOMED RUS LLC, Russia) in 4 capsules 200 mg twice daily (every 12 hours), with the single dose being 800 mg and the daily dose 1600 mg. Duration of treatment was 5 days. The patients were followed up for 28 days. The patients in the standard treatment group (n = 120) received antiviral therapy recommended for outpatients by the provisional guidelines effective at the time of the study. Pathogenetic and symptomatic therapy in both groups was comparable. Results: The results of the clinical study in 240 outpatients with mild or moderate COVID-19 showed that molnupiravir at a dose of 800 mg twice daily for 5 days significantly reduced (by 4-hold at days 1415 of the follow-up) the risk of disease progression to more severe course, compared with the standard therapy group (2.5% (3/120) and 10.0% (12/120) of patients; p = 0.0149.) By days 67 of the follow-up, the virus had been eliminated in 71.67% of the patients treated with the study drug and only in 58.3% (70/120) of the patients in the standard therapy group. Complete clinical recovery at days 67 was achieved in 19.2% (23/120) of the patients in the molnupiravir group, compared to 5.8% (7/120) in the standard therapy group. Compared to the standard therapy, treatment with molnupiravir also significantly reduced the frequency and severity of the disease symptoms, such as cough and change in odor or taste perception over the last 24 hours, already at 67 days after the start of treatment. Molnupiravir treatment was well tolerated, most adverse events were mild. There were no cases of drug withdrawal or dose modification of the study drug due to adverse events. Conclusion: The results of the clinical study of antiviral agent molnupiravir (Esperavir) have proven its benefits over standard therapy in outpatients with mild and moderate COVID-19 in terms of the disease worsening risk reduction and hospitalization, the rate of viral elimination, the changes in symptoms severity over time, improvement of the patients general status and clinical condition and reduction of COVID-19 complications both in patients without and with risk factors for severe COVID-19 outcomes. The results of this study demonstrated a favorable safety profile of molnupiravir in COVID-19 patients.