A randomized, controlled UK trial published today in the Lancet shows that the antiviral drug molnupiravir doesn't prevent COVID-19 hospitalizations or deaths in high-risk, nonhospitalized, vaccinated patients but can speed recovery.
In the open-label trial, a team led by University of Oxford researchers randomly assigned 25,708 high-risk patients infected with the SARS-CoV-2 Omicron variant in a roughly 1:1 ratio to receive either 800 milligrams of oral molnupiravir to take at home twice daily for 5 days or standard care only. Participants completed an online symptom diary every day for 28 days. A total of 94% of all participants had received at least three doses of COVID-19 vaccine.
Average patient age was 56.6 years, and 94% were White. Patients were considered high risk because they were either 50 years and older or had underlying health conditions; all had been ill for 5 days or less before receiving treatment from Dec 8, 2021, to Apr 27, 2022.
Recovery time 4 days shorter
A total of 105 molnupiravir recipients (0.8%) were hospitalized or died, compared with 98 (0.8%) in the control group (adjusted odds ratio, 1.06), demonstrating no benefit, but the molnupiravir group recovered, on average, 4.2 days sooner than controls (9 vs 15 days). In a substudy, the drug also reduced viral detection and load.
Seven control patients hadn't recovered by 28 days. A slightly lower number of molnupiravir patients than controls visited their healthcare provider after the trial ended (20% vs 24%). Fifty molnupiravir patients (0.4%) had serious adverse events, compared with 45 (0.3%) in the usual-care group. No adverse events were considered related to molnupiravir.
The molnupiravir group recovered, on average, 4.2 days sooner than controls (9 vs 15 days).
The researchers noted that previous studies of unvaccinated COVID-19 patients suggested that molnupiravir could help prevent hospitalization in those with mild or moderate illness and that the World Health Organization recommends its use in high-risk patients. But they added that policymakers should consider these new findings when developing infection-control strategies this winter.
The results also have important implications for clinical care, especially considering that molnupiravir is more expensive than the antiviral combination nirmatrelvir-ritonavir Paxlovid ($700 vs $530 per course).
Drug may have other benefits
"Although this trial found no benefit from molnupiravir treatment on its primary outcome… the trial suggests that this treatment could have other benefits when being used to treat COVID-19, such as a faster recovery time and reduced follow up with health services," lead author Chris Butler, MBChB, said in a Lancet news release.
"This could help to ease the burden on UK health services through the treatment of selected patients at home, during times of high disease burden and pressure on key services."
Coauthor Ly-Mee Yu, DPhil, of the University of Oxford, cautioned clinicians against using antivirals when they're not warranted.
"While it's critical to ensure that patients who are likely to benefit treatment with antiviral treatments, such as molnupiravir, receive them; using antivirals to treat patients who are unlikely to benefit carries the risk of further driving antimicrobial resistance, wasting resources, and exposing people to unnecessary harm," she said.
"Our study contributes to the valuable evidence base on who should not be treated with these precious, newly discovered agents, to empower clinicians to make decisions led by robust evidence when prescribing treatments for COVID-19 infections."
In a related commentary, Michael Kidd, MBBS, MD, and Paul Kelly, MBBS, PhD, of the Australian Government Department of Health and Aged Care in Canberra, said the study findings may not apply to the highest-risk COVID-19 patients.
"The shortened and sustained symptom reduction, together with the effects on viral clearance, could be an important consideration in high-risk settings, such as care homes, in terms of potentially minimising the spread of infection among high-risk people," he wrote. "Molnupiravir might also provide benefits to health-care systems, especially during community surges, by potentially allowing health workers to return safely to work sooner."