Tweet
Clin Infect Dis
. 2025 Jul 22:ciaf406.
doi: 10.1093/cid/ciaf406. Online ahead of print. Efficacy and Safety of Obeldesivir in High-Risk Nonhospitalized Patients with COVID-19 (BIRCH): a Phase 3, Randomized, Double-Blind, Placebo-Controlled Study
Anca Streinu-Cercel 1 2 , Antonella Castagna 3 , Shan-Chwen Chang 4 , Yao-Shen Chen 5 , Yiannis Koullias 6 , Afsaneh Mozaffarian 6 , Robert H Hyland 6 , Rita Humeniuk 6 , Luzelena Caro 6 , Santosh Davies 6 , Lauren Rodriguez 6 , Charlotte Hedskog 6 , Shuguang Chen 6 , Kim Etchevers 6 , Nicole Behenna-Renton 7 , Joe Llewellyn 6 , Anu Osinusi 6 , Frank Duff 6 , Alejandro Barrat Hernández 8 , Damien McNally 9 , Jesus Abraham Simon-Campos 10 11 , Fabio Eudes Leal 12 13 , Leon F Fouche 14 , Juan Maria González Del Castillo 15
Affiliations
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 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.
Results: 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.
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.
Clinical trials registration: https://ClinicalTrials.gov NCT05603143; EudraCT 2022-002741-18.
Keywords: COVID-19; SARS-CoV-2; antiviral; obeldesivir.
. 2025 Jul 22:ciaf406.
doi: 10.1093/cid/ciaf406. Online ahead of print. Efficacy and Safety of Obeldesivir in High-Risk Nonhospitalized Patients with COVID-19 (BIRCH): a Phase 3, Randomized, Double-Blind, Placebo-Controlled Study
Anca Streinu-Cercel 1 2 , Antonella Castagna 3 , Shan-Chwen Chang 4 , Yao-Shen Chen 5 , Yiannis Koullias 6 , Afsaneh Mozaffarian 6 , Robert H Hyland 6 , Rita Humeniuk 6 , Luzelena Caro 6 , Santosh Davies 6 , Lauren Rodriguez 6 , Charlotte Hedskog 6 , Shuguang Chen 6 , Kim Etchevers 6 , Nicole Behenna-Renton 7 , Joe Llewellyn 6 , Anu Osinusi 6 , Frank Duff 6 , Alejandro Barrat Hernández 8 , Damien McNally 9 , Jesus Abraham Simon-Campos 10 11 , Fabio Eudes Leal 12 13 , Leon F Fouche 14 , Juan Maria González Del Castillo 15
Affiliations
- PMID: 40694627
- DOI: 10.1093/cid/ciaf406
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 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.
Results: 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.
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.
Clinical trials registration: https://ClinicalTrials.gov NCT05603143; EudraCT 2022-002741-18.
Keywords: COVID-19; SARS-CoV-2; antiviral; obeldesivir.