821Daclatasvir and Asunaprevir Plus Peginterferon Alfa-2a and Ribavirin in Patients With HCV Genotype 1 or 4 Infection: Phase 3 HALLMARK-QUAD Results

Background. Daclatasvir (DCV) is a potent, pangenotypic NS5A inhibitor. Asunaprevir (ASV) is an NS3 protease inhibitor with activity in HCV genotypes (GT) 1 and 4. DCV plus ASV in combination with peginterferon alfa-2a and ribavirin (DCV + ASV + P/R) has previously demonstrated potent antiviral activity in HCV GT 1-infected null responders. This phase 3 study (HALLMARK-QUAD; AI447029) evaluated DCV + ASV + P/R in patients with chronic HCV GT 1 or 4 infection who were prior null or partial responders to peginterferon/ribavirin. Methods. In this open-label study, 354 GT 1 and 44 GT 4-infected patients received 24 weeks of treatment with DCV 60 mg once daily plus ASV 100 mg twice daily in combination with weekly peginterferon alfa-2a 180 µg and weight-based ribavirin twice daily. The primary endpoint was sustained virologic response at posttreatment Week 12 (SVR12). Results. The median age of patients was 53 years, 69% were male, 76% were white, and 23% had cirrhosis; 67% of patients were prior null responders and 33% were partial responders. SVR12 was achieved by 93% of GT 1-infected patients and 98% of GT 4-infected patients; one GT 4 patient was not tested for SVR12 but achieved SVR24, yielding an SVR rate of 100% in GT 4-infected patients (Table). Prior P/R response, cirrhosis status, gender, age, race, or IL28B genotype did not influence SVR12. SVR12 rates for GT 1a were 87% (153/176) vs 99% (176/178) for GT 1b. Serious adverse events occurred in 6% of patients; 5% discontinued treatment due to an adverse event. One death occurred at posttreatment week 12 (pneumonia; not considered related to study therapy). Adverse events occurring in ≥20% of patients were fatigue, headache, pruritus, asthenia, influenza-like illness, insomnia and rash. Grade 3/4 laboratory abnormalities included neutropenia (22%), lymphopenia (16%), anemia (6%), thrombocytopenia (4%) and ALT/AST elevations (3%/3%). Conclusion. The QUAD regimen of DCV + ASV + P/R demonstrated high SVR12 rates of 93% and 100% in GT 1 or GT 4 prior non-responders. DCV + ASV + P/R was generally well tolerated; no additional safety and tolerability concerns were observed compared to P/R regimens. These results support the investigation of DCV in all-oral combinations in multiple patient populations across genotypes. Disclosures. D. M. Jensen, AbbVie: Grant Investigator, Research grant and Research support; Boehringer Ingelheim: Grant Investigator, Research grant and Research support; BMS: Grant Investigator, Research grant and Research support; Roche/Genentech: Grant Investigator, Research grant and Research support; Pharmasset/Gilead: Grant Investigator, Research grant and Research support; Tibotec/Janssen: Grant Investigator, Research grant and Research support K. Sherman, Bristol-Myers Squibb: Investigator, Research grant S. Pol, Bristol-Myers Squibb: Board Member and Investigator, Research grant and Speaker honorarium S. Zeuzem, Bristol-Myers Squibb: Consultant, Consulting fee and Speaker honorarium V. De Ledinghen, AbbVie: Scientific Advisor, Consulting fee; BMS: Scientific Advisor, Consulting fee; Gilead: Scientific Advisor, Consulting fee; Merck: Scientific Advisor, Consulting fee; Janssen: Scientific Advisor, Consulting fee; Echosens: Scientific Advisor, Consulting fee A. Tran, Britsol-Myers Squibb: Investigator, Research grant and Research support M. Elkhashab, Bristol-Myers Squibb: Investigator, Research grant Z. H. Younes, Bristol-Myers Squibb: Investigator, Research grant S. Mauss, Britsol-Myers Squibb: Scientific Advisor, Speaker honorarium G. T. Everson, Bristol-Myers Squibb: Consultant and Investigator, Consulting fee, Research grant and Research support J. Vierling, Abbvie, Biotest, BMS, Gilead, Janssen, Vertex, Merck, Genentech, Genfit, Hyperion, Intercept, Ocera, Sundise: Research Contractor, Research support; Abbvie, Boerhinger-Ingelheim, BMS, Gilead, Janssen, Merck, Hyperion, Intercept, Sundise: Scientific Advisor, Consulting fee M. Brunetto, AbbVie, BMS, Gilead, Janssen, MSD, Roche, Novartis: Speaker's Bureau, Speaker honorarium D. Bernstein, Bristol-Myers Squibb: Investigator, Research grant F. Mcphee, BMS: Employee, Salary D. Hennicken, Bristol-Myers Squibb: Employee, Salary P. Mendez, Bristol-Myers Squibb: Employee, Salary E. Hughes, BMS: Employee, Salary S. Noviello, Bristol-Myers Squibb: Employee and Shareholder, Salary

Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.