Early treatment with Merck's experimental pill molnupiravir nearly halved the risk of hospitalization and death in at-risk, unvaccinated COVID-19 patients, according to interim results from an international phase 3 clinical trial published yesterday in the New England Journal of Medicine (NEJM).
On Nov 30, based in part on an analysis of unpublished data from this MOVe-OUT trial, a Food and Drug Administration (FDA) advisory committee narrowly voted to recommend the use of the drug to treat COVID-19 and prevent hospitalization and death, but the full FDA has yet to grant it an emergency use authorization (EUA). Molnupiravir is already approved for use in the United Kingdom.
If approved for an EUA, the drug would become the first widely available oral pill for US COVID-19 patients that could be taken at home. Current approved treatments require hospital care. Pfizer's Paxlovid is another promising oral COVID-19 drug.
For the new study, which was led by a researcher from IMAT Oncomédica Colombia, the team randomly assigned nonhospitalized, unvaccinated adults with mild to moderate COVID-19, at least one risk factor for severe illness, and symptom onset within the previous 5 days to receive either molnupiravir or a placebo twice daily for 5 days.
Participants were enrolled at 78 sites in 15 countries. Among 1,433 participants in the interim analysis, 716 received molnupiravir, and 717 received placebo.
Hospitalizations, deaths nearly halved
The risk of all-cause hospitalization or death by 29 days was nearly halved in molnupiravir recipients (28 of 385 [7.3%]), relative to placebo (53 of 377 [14.1%]). In an analysis of all randomized participants, 48 of 709 (6.8%) participants in the molnupiravir group were hospitalized or died by 29 days, compared with 68 of 699 (9.7%) in the placebo group.
Subgroup analyses were largely consistent with these overall results, but the point estimate for the difference favored placebo in subgroups of patients who had evidence of a previous COVID-19 infection, low baseline viral load, or diabetes. One molnupiravir patient died, compared with nine placebo participants.
Adverse events occurred in 216 of 710 (30.4%) participants in the molnupiravir group and 231 of 701 (33.0%) in the placebo group. The most common adverse events included COVID-19 pneumonia (6.3% of participants in the molnupiravir group vs 9.6% in the placebo group), diarrhea (2.3% vs 3.0%), bacterial pneumonia (2.0% vs 1.6%), and worsening COVID-19 (7.9% vs 9.8%). The most common treatment-related adverse events included diarrhea (1.7% vs 2.1%), nausea (1.4% vs 0.7%), and dizziness (1.0% vs 0.7%).
The authors noted that molnupiravir could benefit the healthcare system by keeping COVID-19 patients out of the hospital. "Such agents would be important new tools in the COVID-19 treatment armamentarium," they wrote.
In an editorial in the same journal, Richard Whitley, MD, of the University of Alabama at Birmingham, said that COVID-19 pills will not take the place of vaccination. "However, orally bioavailable medications will become an essential tool for physicians in the management of this horrible disease," he wrote.
"The availability of medications with different mechanisms of action offers the opportunity for creating combination therapies that are potentially synergistic and less likely to lead to resistance."
Hope against Omicron
In a Merck news release, study author Monica Gomes, MD, PhD, of the Universidade Federal do Parana in Brazil, said, "One of the hallmarks of the MOVe-OUT study is the diverse patient population, which included adults from 20 countries, with one or more risk factors such as obesity, advanced age, diabetes, and serious heart conditions.
"Based on this study, molnupiravir has the potential to have a meaningful impact for patients, healthcare systems, and public health."
Dean Y. Li, MD, PhD, president of Merck Research Laboratories, expressed hope, based on lab studies, that molnupiravir could be effective against the highly transmissible Omicron (B.1.1.529) variant that now has the world on edge.
He said in the release, "More recent preclinical evidence indicates that molnupiravir has antiviral activity against Omicron, which is encouraging considering the uncertain future of a rapidly evolving virus such as SARS-CoV-2."
CIDRAP Editorial Director Jim Wappes contributed to this story.
