Publication date: Jul 22, 2025

Obeldesivir is an oral nucleoside analog prodrug inhibitor of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Nonhospitalized adults with risk factors for developing severe coronavirus disease 2019 (COVID-19) were enrolled ≤5 days from COVID-19 symptom onset and randomized 1:1 to receive obeldesivir 350 mg or placebo twice daily for 5 days. The primary endpoint was COVID-19-related hospitalization or all-cause death by Day 29. Other endpoints included time to symptom alleviation by Day 15, change in SARS-CoV-2 viral RNA copy number and infectious viral titer, and incidence of adverse events and laboratory abnormalities. 465 participants were randomized and received ≥1 dose of study drug. Baseline characteristics were generally balanced between groups. Overall, 58% had received ≥1 COVID-19 vaccination and 92% were seropositive for SARS-CoV-2 antibodies. COVID-19-related hospitalization or all-cause death by Day 29 was reported in 0/211 (0%) participants with obeldesivir and 1/207 (0. 5%) participants with placebo (log-rank P=0. 32). Time to COVID-19 symptom alleviation was numerically shorter with obeldesivir versus placebo. Obeldesivir reduced viral RNA copy number at Day 5 and infectious titer at Days 3 and 5 versus placebo. The safety profile was generally comparable across arms. Although underpowered in the context of a changing COVID-19 landscape, obeldesivir in nonhospitalized adults with targeted risk factors did not improve COVID-19-related hospitalization or all-cause death. Obeldesivir reduced viral RNA copy number and infectious titer, demonstrating its ability to inhibit SARS-CoV-2 replication, and resulted in numerically faster symptom alleviation. https://ClinicalTrials. gov NCT05603143; EudraCT 2022-002741-18.

Semantics

Original Article