Molnupiravir in the treatment of patients with influenza or acute respiratory viral infections: a multicenter comparative randomized double-blind placebo-controlled trial

The aim. To evaluate the efficacy and safety of molnupiravir compared to placebo in patients with influenza and/or ARVI. Materials and methods. The study involved 300 patients. The study included patients aged 18 to 80 years with clinical signs of influenza/ARVI (duration no more than 48 hours): elevated body temperature ≥37.5℃ and the presence of at least 2 symptoms of moderate severity (chills, headache, myalgia, sore throat, nasal congestion, runny nose, sneezing, cough, with laboratory-confirmed diagnosis of influenza/ARVI at the time of screening), meeting the selection criteria for the study. Group 1 ( n =150) received the investigational medicine molnupiravir (Esperavir®, Promomed Rus LLC, Russia) 800 mg (4 capsules) 2 times/day (daily dose 1600 mg) for 5 days; Group 2 ( n =150) received placebo 4 capsules 2 times/day for 5 days, then patient observation was carried out until day 14 (4 visits after screening). The effectiveness of therapy was assessed according to primary and secondary efficacy criteria. The primary efficacy criterion was the time (in days) to clinical recovery. Safety was assessed by considering the number and severity of adverse events (AEs) and serious adverse events (SAEs). For the analysis of qualitative indicators, an intergroup comparison of proportions was performed using a two-sided version of Fisher's exact test, or the χ2 ("chi-square") test. For quantitative indicators — using the non-parametric Mann-Whitney test. Differences were considered statistically significant at p <0.05. Results . According to the results of the assessment of the primary efficacy criterion, it was shown that molnupiravir therapy statistically significantly reduces the time to clinical recovery compared with placebo ( p =0.000039). According to secondary efficacy criteria, a statistically significant advantage of therapy with the investigational medicine compared with placebo was also demonstrated in terms of the frequency of patients who achieved clinical recovery at Visits 2 and 3 p =0.0110, p =0.0070), the frequency of virus elimination. Even on the 3 rd day of therapy, the frequency of virus elimination in the investigational drug group was 64.7% compared with 40% in the placebo group ( p <0.0001). Statistically significant differences were also shown between the groups in the frequency of patients with the development of ARVI/influenza complications (bronchitis, acute sinusitis, pneumonia, tonsillitis, tracheitis, tracheobronchitis) by Visits 2–4 (Day 3–14) ( p <0.0001), which proves the validity of using targeted antiviral therapy in relation to achieving surrogate therapy endpoints. Therapy with the investigational medicine was characterized by a favorable safety profile. The registered AEs in the molnupiravir and placebo groups belong to the category of expected and did not require drug withdrawal. No SAEs were observed during the study. Conclusion. As a result of the phase III clinical study, the efficacy of molnupiravir (Esperavir®, Promomed Rus LLC, Russia) in the treatment of influenza and/or ARVI and the prevention of the risk of developing complications compared with placebo was proven: patients achieved clinical recovery as early as on the 3rd day of therapy. A favorable safety profile was shown, corresponding to the general characteristics of the medicine.