Efficacy and Safety of Obeldesivir in High-Risk Nonhospitalized Patients with COVID-19 (BIRCH): a Phase 3, Randomized, Double-Blind, Placebo-Controlled Study
MD, PhD Anca Streinu-Cercel, MD Antonella Castagna, MD, PhD Shan-Chwen Chang, MD Yao-Shen Chen, MD Yiannis Koullias, MS Afsaneh Mozaffarian, DPhil Robert H Hyland, PhD Rita Humeniuk, PhD Luzelena Caro, MD Santosh Davies, PhD Lauren Rodriguez, PhD Charlotte Hedskog, PhD Shuguang Chen, MS Kim Etchevers, Nicole Behenna-Renton, Bsc Hons, PharmD Joe Llewellyn, MD, MPH Anu Osinusi, MD Frank Duff, MD Alejandro Barrat Hernández, MB Damien Mcnally, Bch Bao, Jesus Abraham, ; Fabio, MD, PhD Eudes Leal, ; Leon, MBChB F Fouche, ; Juan, Maria González, MD, PhD Del Castillo, Juan Maria González
doi:10.1093/cid/ciaf4061
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-19related 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.
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DOI record:
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"abstract": "<jats:title>Abstract</jats:title>\n <jats:sec>\n <jats:title>Background</jats:title>\n <jats:p>Obeldesivir is an oral nucleoside analog prodrug inhibitor of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).</jats:p>\n </jats:sec>\n <jats:sec>\n <jats:title>Methods</jats:title>\n <jats:p>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.</jats:p>\n </jats:sec>\n <jats:sec>\n <jats:title>Results</jats:title>\n <jats:p>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.</jats:p>\n </jats:sec>\n <jats:sec>\n <jats:title>Conclusions</jats:title>\n <jats:p>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.</jats:p>\n </jats:sec>\n <jats:sec>\n <jats:title>Clinical Trials Registration</jats:title>\n <jats:p>https://ClinicalTrials.gov NCT05603143; EudraCT 2022-002741-18.</jats:p>\n </jats:sec>",
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