Merck and Ridgeback Announce Additional Phase 3 MOVe-OUT Data Showing LAGEVRIO™ (molnupiravir) Reduces Acute Care Visits and Respiratory Interventions in Non-Hospitalized Mild-to-Moderate COVID-19 Patients

News on June 14, 2022 /BioValleyBIOON/ Recently, Merck & Co. and Ridgeback Biotherapeutics announced additional data from the Phase 3 MOVe-OUT clinical trial (NCT04575597). The trial evaluated the oral antiviral drug Lagevrio (molnupiravir) for the treatment of mild to moderate cases at high risk of progressing to severe disease.COVID-19Non-hospitalized adult patients. The analysis shows,Compared with the placebo group, the proportion of acute care visits in the Lagevrio group was lower, and fewer patients required respiratory interventions (including invasive mechanical ventilation).. The relevant data have been published in The Annals of Internal Medicine. See details at:Effect of Molnupiravir on Biomarkers, Respiratory Interventions, and Medical Services in COVID-19FREE。

Analysis of the pre-specified exploratory endpoint showed that,In the modified intent-to-treat (MITT) population, a lower proportion of patients in the Lagevrio treatment group experienced acute care visits or COVID-19-related acute care visits compared to the placebo group.(1) 7.2% of patients in the Lagevrio group reported acute care visits within 29 days, compared to 10.6% in the placebo group, with a relative risk reduction [RRR] of 32.1% (CI: 4.4%-51.7%); (2) 6.6% in the Lagevrio group reported acute care visits related to COVID-19, compared to 10.0% in the placebo group, with an RRR of 33.8% (CI: 5.6%-53.6%). The MITT population includes all randomized subjects who received at least one dose of the study drug and were not hospitalized before the first dose of the study drug.

According to the post-hoc analysis,In the MITT population, fewer patients in the Lagevrio group required respiratory interventions compared to the placebo group (including conventional oxygen therapy, high-flow heated humidification devices, non-invasive mechanical ventilation, or invasive mechanical ventilation)., the RRR for all respiratory interventions was 34.3% (95% CI: 4.3%-54.9%). According to additional post-hoc analyses, in the safety population, the average C-reactive protein (CRP) values decreased earlier and more significantly in the Lagevrio group compared to the placebo group, with earlier and greater improvement in the mean change from baseline in oxygen saturation (SpO2). The safety population includes all randomized participants as well as those who received at least one dose of Lagevrio.

Post-hoc analysis also showed that,In the subgroup of patients hospitalized after randomization, the median time to discharge was 9 days (CI: 7 to 12 days) for patients in the Lagevrio group and 12 days (CI: 9 to 14 days) for the placebo group.Consistent with the MITT population data, post-hoc analysis also indicated that among patients hospitalized after randomization, fewer patients in the Lagevrio group required respiratory interventions compared to the placebo group, with an RRR of 21.3% (95% CI: 0.2%-38.0%) for all respiratory interventions.

Molnupiravir, jointly developed by MSD and Ridgeback Biotherapeutics, is a potent ribonucleoside analog administered orally that inhibits the replication of multiple RNA viruses, including SARS-CoV-2, the pathogen responsible for COVID-19.In November 2021, molnupiravir was approved by the UK Medicines and Healthcare products Regulatory Agency (MHRA).ManagementBureau (MHRA) approved, becomingThe first oral antiviral drug approved for the treatment of COVID-19, This medicine is applicable to: SARS-CoV-2DiagnosisTested positive and having at least one risk factor for severe illnessAdults with Mild to Moderate COVID-19. In the United States,FDAMolnupiravir has been granted Emergency Use Authorization (EUA): For the treatment of adults with mild to moderate COVID-19 who have tested positive for SARS-CoV-2 via direct diagnostic testing and are at high risk of progressing to severe disease (including hospitalization or death), as well as adults with mild to moderate COVID-19 for whom FDA-authorized or approved alternative COVID-19 treatments are not accessible or clinically appropriate.

In addition to the Phase 3 MOVe-OUT trial, the MOVe-AHEAD trial is evaluating molnupiravir forPost-exposurePrevention, a global, multicenter, randomized, double-blind, placebo-controlled Phase 3 study, is evaluating the efficacy and safety of molnupiravir in preventing household transmission of COVID-19.

Chemical Structure of Molnupiravir (Source: scinexx.de)

Molnupiravir is a potent ribonucleoside analog administered orally that inhibits the replication of a variety of RNA viruses, including the novel coronavirus (SARS-CoV-2), which is the pathogen responsible for COVID-19. Molnupiravir has demonstrated activity in several preclinical models of SARS-CoV-2, including for prophylaxis, treatment, and prevention of transmission, and has also shown activity in preclinical models of SARS-CoV-1 and MERS.

MOVe-OUT (NCT04575597) is a global Phase 2/3, randomized, placebo-controlled, double-blind, multi-site study enrolling non-hospitalized adult patients (aged ≥18 years) with laboratory-confirmed mild to moderate COVID-19 who were unvaccinated against SARS-CoV-2, had at least one risk factor associated with poor disease outcomes, and experienced symptoms within 5 days prior to randomization. The Phase 3 portion of the trial was conducted globally, with patients randomized 1:1 to receive either molnupiravir (800mg) or placebo orally twice daily for 5 days. The primary efficacy objective was to evaluate the efficacy of molnupiravir (800mg, orally twice daily for 5 days) versus placebo, as measured by the percentage of patients hospitalized and/or deceased from randomization through Day 29. The most common risk factors for poor disease prognosis in this trial included obesity, older age (>60 years),DiabetesAnd heart disease.

In the analysis of all randomized patients (n=1433) in the MITT population,Molnupiravir Reduced the Risk of Hospitalization or Death: 9.7% (68/699) of patients in the placebo group were hospitalized or died within 29 days after randomization, compared to 6.8% (48/709) in the molnupiravir treatment group, with an absolute risk reduction of 3.0% (95% CI: 0.1, 5.9). There were 9 deaths in the placebo group and 1 death in the molnupiravir group.

The determination of the primary efficacy was based on a planned interim analysis of 762 patients.In the interim analysis, molnupiravir reduced the relative risk of hospitalization or death by approximately 50% compared to placebo.In the molnupiravir group, 7.3% (28/385) of patients were hospitalized or died between randomization and Day 29, compared to 14.1% (53/377) in the placebo group, with an absolute risk reduction of 6.8% (95% CI: 2.4-11.3; p=0.0024). By Day 29, no deaths were reported in the molnupiravir treatment group, while there were 8 deaths in the placebo group.

The safety of molnupiravir is based on the safety analysis assessment of 1,411 non-hospitalized COVID-19 patients who were randomized to receive either molnupiravir (n=710) or placebo (n=701) for 5 days in the MOVe-OUT trial. The most common (incidence ≥1%) adverse events in the molnupiravir treatment group were diarrhea (2% in the molnupiravir group vs. 2% in the placebo group), nausea (1% in the molnupiravir group vs. 1% in the placebo group), and dizziness (1% in the molnupiravir group vs. 1% in the placebo group). Fewer patients discontinued study intervention due to adverse events in the molnupiravir group (1%) compared to the placebo group (3%). Serious adverse event rates were 7% in the molnupiravir group and 10% in the placebo group. The most serious adverse events were related to COVID-19. (Bioon.com)

Source of the original text:Merck and Ridgeback Announce New Data For Investigational LAGEVRIO™ (molnupiravir) From Phase 3 MOVe-OUT Study