Abstract
Background
COVID-19 continues to cause morbidity. Obeldesivir (ODV) is an oral, broad spectrum, nucleoside analog prodrug inhibitor of SARS-CoV-2 RNA-dependent RNA polymerase.
Methods
OAKTREE was a Phase 3, randomized, double-blind, placebo (PBO)-controlled study in adults and adolescents without risk factors for progression to severe COVID-19. Participants were enrolled within 3 days of COVID-19 symptom onset and randomized 1:1 to receive 350 mg of ODV or PBO twice a day for 5 days. Primary endpoints were time to symptom alleviation (9 symptoms; first of 48 consecutive hours) by Day 29 and incidence of adverse events (AEs) and laboratory abnormalities. Secondary endpoints included symptom resolution and viral kinetics.
Results
1955 participants were enrolled (Feb 13-Oct 31, 2023), randomized, and received ≥1 dose of study drug (98% completed study drug and the study). Baseline characteristics were similar between groups (overall mean age 41 years, 59% female, 93% Hispanic or Latino, 87% White, 11% Black, and 2% Asian). Seropositivity was >99% for SARS-CoV-2 (anti-S or anti-N) antibodies, 73% were vaccinated, and mean baseline SARS-CoV-2 viral load was 5.09 log10 copies/mL. The efficacy analysis set consisted of 1768 participants with PCR-confirmed SARS-CoV-2 at baseline. The Kaplan-Meier estimate of median time to symptom alleviation was 5.9 days (95% CI, 5.4-6.1) with ODV and 6.0 days (95% CI, 5.8-6.3) with PBO (P = 0.068). Times to symptom resolution were similar (ODV: 9.2 days [95% CI 8.9-10.0]; PBO: 9.3 days [95% CI 8.9-10.1]; P = 0.56). ODV reduced viral load at Days 3 and 5, with least squares mean treatment differences of -0.31 (P < 0.0001) and -0.18 (P = 0.0037) log10 copies/mL, respectively. The safety profile of ODV was similar to PBO, with similar rates of AEs, treatment-related AEs, serious AEs, and AEs leading to study drug discontinuation. No deaths or hospitalizations were reported by Day 29.
Conclusion
ODV was generally safe and well tolerated but did not significantly reduce time to symptom alleviation or resolution in a standard risk population with >99% SARS-CoV-2 seropositivity. ODV reduced SARS-CoV-2 viral load at Days 3 and 5 compared to PBO. Symptom duration was markedly shorter than in prior trials, consistent with milder disease in a population with high rates of hybrid immunity.
Disclosures
Onyema Ogbuagu, MD, Gilead Sciences, Inc.: Advisor/Consultant|Gilead Sciences, Inc.: Honoraria|GSK/ViiV: Advisor/Consultant|GSK/ViiV: Honoraria|Janssen: Advisor/Consultant|Moderna: Advisor/Consultant|Moderna: Honoraria Jason D. Goldman, MD, MPH, Gilead Sciences, Inc.: Advisor/Consultant|Gilead Sciences, Inc.: Grant/Research Support|Gilead Sciences, Inc.: Speaker|Helix: Grant/Research Support Robert L. Gottlieb, MD, AbbVie: Advisor/Consultant|AbCellera: Stocks/Bonds (Public Company)|AstraZeneca: Advisor/Consultant|Eli Lilly: Advisor/Consultant|Gilead Sciences Inc.: Advisor/Consultant|Gilead Sciences Inc.: Honoraria|Gilead Sciences Inc.: travel support, gift-in-kind to his institution to facilitate an unrelated academic-sponsored clinical trial NCT03383419|GSK Pharmaceuticals: Advisor/Consultant|Johnson & Johnson: Advisor/Consultant|Pfizer: Honoraria|Regeneron: Grants or contracts to institution|Roche: Advisor/Consultant|Roivant Sciences (Kinevant Sciences): Grants or contracts to institution Upinder Singh, MD, FIDSA, Gilead Sciences, Inc.: Advisor/Consultant|Pfizer: Grant/Research Support|Regeneron: Advisor/Consultant Masaharu Shinkai, MD, PhD, AstraZeneca: Grant/Research Support|AstraZeneca: Lecture fees|Fujifilm: Grant/Research Support|Genova Inc: Grant/Research Support|Gilead Sciences, Inc.: Grant/Research Support|GSK: Grant/Research Support|GSK: Lecture fees|Kyorin Pharmaceutical: Lecture fees|Pfizer: Grant/Research Support|Sanofi: Grant/Research Support|Sanofi: Lecture fees|Shionogi: Grant/Research Support Dahlene Fusco, MD, PhD, AICURIS: Site PI|Gilead Sciences, Inc.: Advisor/Consultant|Gilead Sciences, Inc.: Site PI|Metro Biotech: Site PI|Regeneron: Site PI|The Biomedical Advanced Research and Development Authority (BARDA) and the National Institute of Allergy and Infectious Diseases (NIAID): Site PI Erika Gonzalez, MD, AstraZeneca: Clinical research PI; Business relationship|DBV: Clinical research PI; Business relationship|Genentech: Clinical research PI; Business relationship|Novartis: Clinical research PI; Business relationship|Regeneron: Clinical research PI; Business relationship Princy N. Kumar, MD, Gilead Sciences, Inc.: Advisor/Consultant|Gilead Sciences, Inc.: Board Member|Gilead Sciences, Inc.: Grant/Research Support|Gilead Sciences, Inc.: Medical writing support provided by Aspire Scientific (Bollington, UK)|Gilead Sciences, Inc.: Stocks/Bonds (Public Company)|Johnson & Johnson: Stocks/Bonds (Public Company)|Merck: Advisor/Consultant|Merck: Board Member|Merck: Grant/Research Support|Merck: Stocks/Bonds (Public Company)|Moderna: Stocks/Bonds (Public Company)|Pfizer: Stocks/Bonds (Public Company)|Theratechnologies: Grant/Research Support|ViiV/GSK: Advisor/Consultant|ViiV/GSK: Board Member|ViiV/GSK: Grant/Research Support|ViiV/GSK: Stocks/Bonds (Public Company) Annie Luetkemeyer, MD, Cepheid: Grant/Research Support|Gilead Sciences, Inc.: Grant/Research Support|GSK: Grant/Research Support|Merck: Grant/Research Support|ViiV: Grant/Research Support|Vir: Advisor/Consultant Amos Lichtman, MPH, MD, Gilead Sciences, Inc.: Employee|Gilead Sciences, Inc.: Stocks/Bonds (Public Company) Afsaneh Mozaffarian, MS, Gilead Sciences, Inc.: Employee|Gilead Sciences, Inc.: Stocks/Bonds (Public Company) Yiannis Koullias, MD, Gilead Sciences, Inc.: Employee|Gilead Sciences, Inc.: Stocks/Bonds (Public Company) Robert H. Hyland, DPhil, Gilead Sciences, Inc.: Employee|Gilead Sciences, Inc.: Stocks/Bonds (Public Company) Joe Llewellyn, PharmD, Gilead Sciences, Inc.: Employee|Gilead Sciences, Inc.: Stocks/Bonds (Public Company) Anu Osinusi, MD, Gilead Sciences, Inc.: Employee|Gilead Sciences, Inc.: Stocks/Bonds (Public Company) Frank Duff, MD, Gilead Sciences, Inc.: Employee|Gilead Sciences, Inc.: Stocks/Bonds (Public Company) Rita Humeniuk, PhD, Gilead Sciences, Inc.: Former Employee|Gilead Sciences, Inc.: Stocks/Bonds (Public Company) Luzelena Caro, PhD, Gilead Sciences, Inc.: Employee|Gilead Sciences, Inc.: Stocks/Bonds (Public Company) Santosh Davies, MD, Gilead Sciences, Inc.: Employee|Gilead Sciences, Inc.: Stocks/Bonds (Public Company) Charlotte Hedskog, PhD, Gilead Sciences, Inc.: Employee|Gilead Sciences, Inc.: Stocks/Bonds (Public Company) Shuguang Chen, PhD, Gilead Sciences, Inc.: Employee|Gilead Sciences, Inc.: Stocks/Bonds (Public Company) Kim Etchevers, MS, Gilead Sciences, Inc.: Employee|Gilead Sciences, Inc.: Stocks/Bonds (Public Company) Priyanka Nadig, MPH, Gilead Sciences, Inc.: Employee|Gilead Sciences, Inc.: Stocks/Bonds (Public Company) Anita Kohli, MD, Eli Lilly: Received clinical trial revenue|Gilead Sciences, Inc.: Advisor/Consultant|Gilead Sciences, Inc.: Received clinical trial revenue|Vir: Received clinical trial revenue