Secondary Analysis of Molnupiravir Trial for Shows Additional Benefits for COVID-19 Patients

Nonhospitalized patients with COVID-19 who took the antiviral drug molnupiravir were less likely to need respiratory interventions and had fewer acute care visits, a secondary analysis of the phase 3 trial found.

The study, published in the Annals of Internal Medicine, included 1433 nonhospitalized patients at 107 sites around the world who received either 800 mg of molnupiravir or a placebo every 12 hours for 5 days.

“The findings suggest there are additional important clinical benefits of molnupiravir beyond reduction in hospitalization and death,” the study authors, led by Matthew Johnson, MD, of Merck, wrote.

Molnupiravir, invented at Drug Innovations at Emory (DRIVE) and developed by Merck and Ridgeback Biotherapeutics, was granted an Emergency Use Authorization (EUA) by the Food and Drug Administration (FDA) for the treatment of COVID-19 in December. The approval came one day after the FDA granted an EUA for Pfizer’s antiviral Paxlovid as the first oral antiviral for treating COVID-19.

The MOVe-OUT trial showed molnupiravir reduced patient risk of COVID-19 hospitalization or death by approximately 50%.

The secondary analysis of the randomized controlled clinical trial, MOVe-OUT, included patients with mild to moderate COVID-19 and risk factors for progressing to severe disease. Investigators analyzed the effects of molnupiravir on biomarkers, respiratory interventions and medical services.

Participants in the molnupiravir group saw faster normalization of C-reactive protein (CRP) concentration and oxygen saturation (SpO2) compared with those in the placebo group by Day 29. Improvements began on Day 3 of treatment and continued through Day 29.

“The continuous decreases in CRP concentration and increases in SpO2 with molnupiravir indicate subsiding systemic inflammation and recovering respiratory function,” the authors wrote.

The relative risk reduction for requiring the use of respiratory interventions was 34.3% among the patients in the treatment group. Those who received molnupiravir also had RRRs of 23.5% for conventional oxygen therapy, 26.1% for high-flow heated and humidified oxygen treatment, 75.4% for noninvasive mechanical ventilation, 64.1% for invasive mechanical ventilation.

“The decreased need for invasive mechanical ventilation is particularly relevant because patients with COVID-19 who receive this respiratory intervention have mortality rates up to 50%,” the authors wrote.

Among a subgroup of patients who required hospitalization, the RRR for all respiratory interventions was 21.3%. The median number of days before discharge also was lower among the treatment group – 9, compared with 12 for those in the placebo group.

Those in the treatment group had an RRR for acute care visits of 32.1% and 33.8% for COVID-19-related acute care visits.

“Altogether, these findings suggest there is added clinical value of molnupiravir for the treatment of nonhospitalized adults with mild to moderate COVID-19,” the authors wrote. “Meaningful benefits of molnupiravir to patients and health care systems may exceed the previously demonstrated benefits of reducing hospitalizations or death due to disease progression as well as alleviating symptoms in high-risk patients.”

Limitations of the study include that analysis was conducted retrospectively, despite the data being collected prospectively for the MOVe-OUT trial. The study also didn’t include any vaccinated patients, so it could not assess the possible impact of vaccination or the time elapsed since vaccination on findings. Potential financial impact was not assessed.