Merck Inc., + Ridgeback Biotherapeutics provide update on progress of clinical development program for molnupiravir, an investigational oral antiviral for the treatment of mild-to-moderate COVID-19.

Merck Inc., and Ridgeback Biotherapeutics provided an update on the clinical development program for molnupiravir (MK-4482/ EIDD-2801), an investigational orally available antiviral therapeutic. Based on a planned interim analysis of data from the Phase II, dose-finding portion (Part 1) of two ongoing placebo-controlled Phase II/III trials evaluating molnupiravir administered twice a day for five days in outpatients (MOVe-OUT) and hospitalized patients (MOVe-IN) with COVID-19, and from a previously completed Phase IIa dose-ranging study in outpatients, the decision has been made to proceed with the Phase III portion (Part 2) of MOVe-OUT in outpatients with COVID-19, evaluating the 800 mg dose of molnupiravir twice daily. Data from MOVe-IN indicate that molnupiravir is unlikely to demonstrate a clinical benefit in hospitalized patients, who generally had a longer duration of symptoms prior to study entry; therefore, the decision has been made not to proceed to Phase III. Update on MOVe-OUT (MK-4482-002) and MOVe-IN (MK-4482-001) : MOVe-OUT is an ongoing Phase II/III, randomized, placebo-controlled, double-blind, multi-site study evaluating the efficacy, safety and pharmacokinetics of orally administered molnupiravir in non-hospitalized participants with COVID-19 confirmed using polymerase chain reaction. The primary efficacy objective of MOVe-OUT is to evaluate the efficacy of molnupiravir compared to placebo as assessed by the percentage of patients who are hospitalized and/or die from the time of randomization through Day 29. Part 1 of MOVe-OUT enrolled a total of 302 participants, with symptom onset within seven days prior to randomization, who were assigned to receive molnupiravir 200 mg (75), 400 mg (77), or 800 mg (76), or placebo (74). The percentage of patients who were hospitalized and/or died in Part 1 of the MOVe-OUT study was lower in the combined molnupiravir-treated groups versus the placebo arm; the number of events reported are not sufficient to provide a meaningful measure of clinical effect. Analysis of SARS-CoV-2 in nasopharyngeal and oropharyngeal swabs from patients in both MOVe-OUT and MOVe-IN using quantitative and qualitative polymerase chain reaction, an exploratory endpoint, indicated that molnupiravir inhibits replication of the virus, as demonstrated by a greater decrease from baseline in viral RNA compared to placebo at Day 5 and Day 10, and by a larger proportion of participants with undetectable viral RNA at Day 10 and Day 15 following the end of treatment. The largest overall magnitude of antiviral effect was observed in the 800 mg dose compared with the 200 mg and 400 mg doses. These differences in virology endpoints were more pronounced in participants enrolled less than 5 days following symptom onset. Among 299 patients who received at least one dose of study intervention in MOVe-OUT, 6.2% (14/225) of those receiving molnupiravir and 6.8% (5/74) of those receiving placebo reported drug-related adverse events. In MOVe-IN, of 293 patients who received at least one dose of study intervention, 11.0% (24/218) of those treated with molnupiravir and 21.3% (16/75) of those receiving placebo reported drug-related adverse events. To date, safety and laboratory data from MOVe-IN and MOVe-OUT provide no evidence for unexpected findings or trends observed at any of the doses studied. In both trials, no deaths were considered drug-related by the investigators, and there were no drug-related adverse events that led to discontinuation in participants who received molnupiravir. Interim results from both MOVe-IN and MOVe-OUT, including virology findings and pharmacokinetic analyses, have been shared with regulatory authorities and will be presented at an upcoming medical meeting. The external Data Monitoring Committee noted that the subgroup analyses support potential benefit of treatment and suggested amendments to the MOVe-OUT protocol to focus enrollment on patients early in the course of disease and those considered high risk for poor COVID-19 outcomes (e.g., older patients, those with obesity and diabetes). Based upon these recommendations, Merck Inc., will amend the inclusion criteria for MOVe-OUT by reducing the allowable symptom duration for enrollment to less than 5 days and by enrolling participants with at least one risk factor for progression to severe disease. Merck plans to start enrolling patients in Phase III portion (Part 2) of MOVe-OUT by late April/early May. Final data from the Phase III portion (Part 2) of the MOVe-OUT study is estimated to be available in September/ October 2021. Merck currently anticipates that, pending favorable results from MOVe-OUT, the earliest possible submission for an Emergency Use Authorization for molnupiravir will be in the second half of 2021. Merck and Ridgeback Biotherapeutics plan to share further findings from the ongoing molnupiravir development program with regulatory agencies as they become available.In addition, Merck plans to initiate a clinical program to evaluate molnupiravir for post- exposure prophylaxis in the second half of 2021.