Based on an interim analysis of data from the phase 2, dose-finding portion (Part 1) of 2 ongoing phase 2/3 trials evaluating molnupiravir, Merck and Ridgeback Biotherapeutics have decided to halt the MOVe-IN study for hospitalized COVID-19 patients and proceed with the phase 3 portion (Part 2) of the MOVe-OUT study in outpatients with COVID-19.
MOVe-OUT is a randomized, placebo-controlled, double-blind phase 2/3 study (ClinicalTrials.gov: NCT04575597) investigating the efficacy and safety of molnupiravir, an investigational, oral antiviral, in non-hospitalized patients 18 years of age and older with confirmed COVID-19 and symptom onset within 7 days prior to randomization. The phase 2 portion (Part 1) of the study included 302 patients who were randomly assigned 1:1:1:1 to receive molnupiravir 200mg, 400mg, 800mg, or placebo twice daily for 5 days.
Findings from Part 1 of the MOVe-OUT study showed that compared with placebo, the percentage of patients who were hospitalized and/or died was lower in the combined molnupiravir arms. However, due to an insufficient number of events reported, a meaningful measure of clinical effect could not be ascertained.
Data from both the MOVe-OUT and MOVe-IN (ClinicalTrials.gov: NCT04575584) trials also demonstrated that molnupiravir appears to inhibit replication of the virus. Compared with placebo, a greater decrease in viral RNA was observed in molnupiravir-treated patients at day 5 and day 10. Additionally, a greater proportion of patients treated with molnupiravir had undetectable viral RNA at day 10 and day 15. The antiviral effect was larger with the 800mg dose compared with the 200mg and 400mg doses.
Based on recommendations from an external data monitoring committee, the inclusion criteria for the phase 3 portion of the MOVe-OUT study will be updated to include patients with symptom duration of 5 days or less and at least 1 risk factor for progression to severe disease. Merck will begin enrolling patients in the phase 3 portion (Part 2) of the MOVe-OUT study by late April/early May of 2021 and expects to have study data available in September/October of 2021.
“Data from the dose-finding portion of these studies are consistent with the mechanism of action and provide meaningful evidence for the antiviral potential of the 800mg dose,” said Dr Roy Baynes, senior vice president and head of global clinical development, chief medical officer, Merck Research Laboratories. “Based on the findings of this study we are advancing a phase 3 trial program in non-hospitalized patients that strategically leverages our large network of clinical sites to enroll appropriate patients globally.”
According to the Companies, data from the MOVe-IN study indicate that molnupiravir is unlikely to demonstrate a clinical benefit in hospitalized patients. These patients generally had a longer duration of symptoms prior to study entry.
Merck has also decided to discontinue its development of MK-7110 (formerly known as CD24Fc) for the treatment of hospitalized patients with COVID-19. The decision to halt development was made following a request from the Food and Drug Administration for additional supporting data that would not be expected to be available until the first half of 2022.
- Merck and Ridgeback Biotherapeutics provide update on progress of clinical development program for molnupiravir, an investigational oral therapeutic for the treatment of mild-to-moderate COVID-19. [press release]. Kenilworth, NJ & Miami, FL: Merck and Ridgeback Biotherapeutics; April 15, 2021.
- Merck to discontinue development of MK-7110 for COVID-19. [press release]. Kenilworth, NJ: Merck; April 15, 2021.