Nirmatrelvir-Ritonavir May Not Benefit Patients at Standard Risk for Severe COVID-19

Treatment with nirmatrelvir-ritonavir did not significantly shorten the time to sustained alleviation of symptoms in patients with COVID-19 compared with placebo, according to a study published in The New England Journal of Medicine.

The phase 2-3 trial focused on patients fully vaccinated against COVID-19 with at least one risk factor for severe disease and patients without risk factors who had not received a COVID-19 vaccine within the previous year. Researchers randomized 1296 adults with COVID-19 symptom onset within the past 5 days 1:1 to nirmatrelvir-ritonavir or placebo every 12 hours for 5 days.

Among the 1296 participants included in the full analysis population, 654 received at least one dose of nirmatrelvir-ritonavir and 634 received at least one dose of placebo and had at least one postbaseline visit.

Sustained alleviation of all targeted signs and symptoms of COVID-19 occurred at a median 12 days in the nirmatrelvir-ritonavir group and 13 days in the placebo group. Rates of hospitalization for COVID-19 or death from any cause were 0.8% in the nirmatrelvir-ritonavir group and 1.6% in the placebo group.

Adverse events affected 25.8% of participants in the nirmatrelvir-ritonavir group and 24.1% in the placebo group. The most commonly reported treatment-related adverse events in the nirmatrelvir-ritonavir group were dysgeusia and diarrhea, which affected a respective 5.8% and 2.1% of participants.

“Nirmatrelvir-ritonavir was not associated with a significantly shorter time to sustained alleviation of COVID-19 symptoms than placebo, and the usefulness of nirmatrelvir-ritonavir in patients who are not at high risk for severe COVID-19 has not been established,” wrote first author Jennifer Hammond, PhD, of Pfizer, Collegeville, Pennsylvania, and study coauthors.

Reference

Hammond J, Fountaine RJ, Yunis C, et al. Nirmatrelvir for vaccinated or unvaccinated adult outpatients with Covid-19. N Engl J Med. 2024;390(13):1186-1195. doi:10.1056/NEJMoa2309003