tetano
Editor, Senior Moderator
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[SUP] 1 2 [/SUP], Antonella Castagna[SUP] 3 [/SUP], Shan-Chwen Chang[SUP] 4 [/SUP], Yao-Shen Chen[SUP] 5 [/SUP], Yiannis Koullias[SUP] 6 [/SUP], Afsaneh Mozaffarian[SUP] 6 [/SUP], Robert H Hyland[SUP] 6 [/SUP], Rita Humeniuk[SUP] 6 [/SUP], Luzelena Caro[SUP] 6 [/SUP], Santosh Davies[SUP] 6 [/SUP], Lauren Rodriguez[SUP] 6 [/SUP], Charlotte Hedskog[SUP] 6 [/SUP], Shuguang Chen[SUP] 6 [/SUP], Kim Etchevers[SUP] 6 [/SUP], Nicole Behenna-Renton[SUP] 7 [/SUP], Joe Llewellyn[SUP] 6 [/SUP], Anu Osinusi[SUP] 6 [/SUP], Frank Duff[SUP] 6 [/SUP], Alejandro Barrat Hernández[SUP] 8 [/SUP], Damien McNally[SUP] 9 [/SUP], Jesus Abraham Simon-Campos[SUP] 10 11 [/SUP], Fabio Eudes Leal[SUP] 12 13 [/SUP], Leon F Fouche[SUP] 14 [/SUP], Juan Maria González Del Castillo[SUP] 15 [/SUP]
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[SUP] 1 2 [/SUP], Antonella Castagna[SUP] 3 [/SUP], Shan-Chwen Chang[SUP] 4 [/SUP], Yao-Shen Chen[SUP] 5 [/SUP], Yiannis Koullias[SUP] 6 [/SUP], Afsaneh Mozaffarian[SUP] 6 [/SUP], Robert H Hyland[SUP] 6 [/SUP], Rita Humeniuk[SUP] 6 [/SUP], Luzelena Caro[SUP] 6 [/SUP], Santosh Davies[SUP] 6 [/SUP], Lauren Rodriguez[SUP] 6 [/SUP], Charlotte Hedskog[SUP] 6 [/SUP], Shuguang Chen[SUP] 6 [/SUP], Kim Etchevers[SUP] 6 [/SUP], Nicole Behenna-Renton[SUP] 7 [/SUP], Joe Llewellyn[SUP] 6 [/SUP], Anu Osinusi[SUP] 6 [/SUP], Frank Duff[SUP] 6 [/SUP], Alejandro Barrat Hernández[SUP] 8 [/SUP], Damien McNally[SUP] 9 [/SUP], Jesus Abraham Simon-Campos[SUP] 10 11 [/SUP], Fabio Eudes Leal[SUP] 12 13 [/SUP], Leon F Fouche[SUP] 14 [/SUP], Juan Maria González Del Castillo[SUP] 15 [/SUP]
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.