Efficacy and Safety of Obeldesivir in High-Risk Nonhospitalized Patients With COVID-19 (BIRCH): A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study.
Journal
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
Journal Volume
82
Journal Issue
1
Start Page
e24
End Page
e32
ISSN
1537-6591
Date Issued
2026-02-09
Author(s)
Streinu-Cercel, Anca
Castagna, Antonella
Chen, Yao-Shen
Koullias, Yiannis
Mozaffarian, Afsaneh
Hyland, Robert H
Humeniuk, Rita
Caro, Luzelena
Davies, Santosh
Rodriguez, Lauren
Hedskog, Charlotte
Chen, Shuguang
Etchevers, Kim
Behenna-Renton, Nicole
Llewellyn, Joe
Osinusi, Anu
Duff, Frank
Barrat Hernández, Alejandro
McNally, Damien
Simon-Campos, Jesus Abraham
Leal, Fabio Eudes
Fouche, Leon F
González Del Castillo, Juan Maria
Abstract
Background. Obeldesivir is an oral nucleoside analog prodrug inhibitor of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Methods. 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 end point was COVID-19–related hospitalization or all-cause death by day 29. Other end points 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. Results. Four hundred and sixty five 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 of 211 (0%) participants with obeldesivir and 1 of 207 (0.5%) participants with placebo (log-rank P =.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. Conclusions. 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.
Subjects
COVID-19
SARS-CoV-2
antiviral
obeldesivir
Type
journal article