Merck, known as MSD outside the United States and Canada, and Ridgeback Biotherapeutics today announced the Annals of Internal Medicine has published additional data from the Phase 3 MOVe-OUT trial evaluating LAGEVRIO™ (molnupiravir), an investigational oral antiviral medicine, in non-hospitalized adults with mild to moderate COVID-19 who were at high risk for progressing to severe disease.
Analyses of pre-specified exploratory endpoints indicate that a lower proportion of LAGEVRIO-treated participants in the modified intent-to-treat (MITT) population had an acute care visit or a COVID-19-related acute care visit versus placebo-treated participants in the MITT population: 7.2% of participants who received LAGEVRIO reported an acute care visit through Day 29, versus 10.6% of placebo participants, with a relative risk reduction [RRR] of 32.1% [CI, 4.4% to 51.7%]; 6.6% of participants who received LAGEVRIO reported a COVID-19-related acute care visit, versus 10.0% of placebo participants, with a RRR of 33.8% [CI, 5.6% to 53.6%]. The MITT population included all participants who were randomly assigned, received at least one dose of study drug, and were not hospitalized before the first dose of study drug. Based on a post hoc analysis, fewer LAGEVRIO-treated participants in the MITT population required respiratory interventions (including conventional oxygen therapy, a high-flow heated and humidified device, noninvasive mechanical ventilation, or invasive mechanical ventilation) versus placebo-treated participants, with a RRR of 34.3% [95% CI, 4.3% to 54.9%] for all respiratory interventions. Based on additional post hoc analyses, participants in the safety population who received LAGEVRIO showed earlier and larger reductions in mean C-reactive protein (CRP) values, and earlier and larger improvements in mean change from baseline oxygen saturation (SpO2) values, compared with participants who received placebo. The safety population consisted of all participants who had undergone randomization and had received at least one dose of LAGEVRIO.
Post hoc analyses also suggest that among the subgroup of participants who were hospitalized after randomization in MOVe-OUT, the median time to hospital discharge was nine days [CI, 7 to 12 days] for participants who received LAGEVRIO, versus 12 days [CI, 9 to 14 days] in the placebo group. Consistent with the full MITT population data, post hoc analyses also suggest that fewer LAGEVRIO-treated participants who were hospitalized after randomization required respiratory interventions versus placebo-treated participants, with a RRR of 21.3% [95% CI, 0.2% to 38.0%] for all respiratory interventions.
“The analyses add to our understanding of the clinical profile of LAGEVRIO and help to reinforce the importance of LAGEVRIO as part of the response to the COVID-19 pandemic,” said Dr. Dean Y. Li, president, Merck Research Laboratories.
“The primary data from MOVe-OUT demonstrated a significant reduction in the risk for progression to severe COVID-19, including hospitalization and death, when compared to placebo among non-hospitalized, at-risk patients. In light of the continued burden of COVID-19, we are encouraged by these new data,” said Wendy Holman, chief executive officer, Ridgeback Biotherapeutics. “We look forward to continuing to study LAGEVRIO with the goal of helping high-risk patients and overburdened healthcare systems globally continue to combat the COVID-19 pandemic.”
In addition to the MOVe-OUT trial, LAGEVRIO is being evaluated for post-exposure prophylaxis in MOVe-AHEAD, a global, multicenter, randomized, double-blind, placebo-controlled Phase 3 study evaluating the efficacy and safety of LAGEVRIO in preventing the spread of COVID-19 within households.
About the MOVe-OUT Study
The Phase 3 MOVe-OUT clinical trial (NCT04575597) evaluated LAGEVRIO (molnupiravir) 800 mg twice-daily in non-hospitalized, unvaccinated adult patients with laboratory-confirmed mild to moderate COVID-19, symptom onset within five days of study randomization, and at least one risk factor associated with poor disease outcomes (e.g. heart disease, diabetes). The primary efficacy objective of MOVe-OUT was to evaluate the efficacy of LAGEVRIO 800 mg twice-daily for five days compared to placebo as assessed by the percentage of participants who were hospitalized and/or died through Day 29. These findings were published in the New England Journal of Medicine.
In analyses from all randomized patients (n=1433) in the MITT population, LAGEVRIO reduced the risk of hospitalization or death: 9.7% (68/699) of patients in the placebo group were hospitalized or died through Day 29 compared to 6.8% (48/709) of patients who received LAGEVRIO, for an absolute risk reduction of 3.0% (95% confidence interval [CI]: 0.1, 5.9). Nine deaths were reported in the placebo group, and one in the LAGEVRIO group.
The determination of primary efficacy was based on a planned interim analysis of 762 participants. At the interim analysis, treatment with LAGEVRIO significantly reduced the risk for hospitalizations and death through Day 29 following randomization: 14.1% (53/377) of patients in the placebo group were hospitalized or died, compared to 7.3% (28/385) of patients who received LAGEVRIO. The absolute risk reduction between the LAGEVRIO and the placebo arm was 6.8 percentage points (95% CI: 2.4, 11.3; p=0.0024).
The safety of LAGEVRIO was evaluated based on an analysis of MOVe-OUT in which 1,411 non-hospitalized subjects with COVID-19 were randomized and treated with LAGEVRIO (N=710) or placebo (N=701) for up to 5 days. Adverse events were those reported while subjects were on study intervention or within 14 days of study intervention completion/discontinuation. The most common adverse reactions for LAGEVRIO (incidence ≥1%) were diarrhea (2% for LAGEVRIO, 2% for placebo), nausea (1% for LAGEVRIO, 1% for placebo) and dizziness (1% for LAGEVRIO, 1% for placebo). Discontinuation of study intervention due to an adverse event (AE) occurred in 1% of subjects receiving LAGEVRIO and 3% of subjects receiving placebo. Serious AEs occurred in 7% of subjects receiving LAGEVRIO and 10% receiving placebo; most serious AEs were COVID-19 related.
