WASHINGTON — Patients with chronic hepatitis C genotype 1, including those with cirrhosis, experienced high rates of sustained virologic response at 12 weeks post-treatment with a safe, well-tolerated, interferon- and ribavirin-free regimen of three direct-acting antivirals in a study presented at The Liver Meeting.
In a phase 2b, open-label study, researchers randomly assigned 166 patients to triple therapy with NS5A inhibitor daclatasvir, NS3 inhibitor asunaprevir and 75 mg (n=80) or 150 mg (n=86) non-nucleoside NS5B inhibitor BMS-791325 for 12 weeks. All patients were treatment naive, had HCV genotype 1, and 9% of the cohort had biopsy-confirmed cirrhosis. Eighty-two percent of patients had genotype 1a, 67% had a non-CC IL28B genotype and 38% had a METAVIR fibrosis stage of F3 or F4. SVR at 12 weeks post-treatment was the primary endpoint.
End-of-treatment response occurred in 97.5% of the 75-mg group and 94.2% of the 150-mg group. SVR at 12 weeks was approximately 92% across the cohort, with no significant impact observed as a result of BMS-791325 dosage. Among cirrhotic patients, overall rates of SVR12 were more than 90%, regardless of genotype 1 subtype or IL28B status.
Gregory T. Everson
Virologic breakthrough occurred in two patients in the 75-mg group and three in the 150-mg group. Relapse occurred in four 75-mg patients and in two 150-mg recipients, all within 4 weeks of treatment initiation. All patients who experienced virologic failure had genotype 1a; no other characteristics at baseline were associated with breakthrough.
Treatment was well tolerated in both groups. No patients discontinued treatment because of treatment-related serious adverse events, and symptoms while on treatment were mild or moderate in all but one patient who developed an AST elevation of grade 3-4 that later normalized, and one cirrhotic patient who experienced an elevation in bilirubin.
“This looks like a fairly good regimen: It’s a 12-week course of therapy, interferon-free, ribavirin-free, all-oral, three DAAs, and achieves an SVR12 in over 90% of treated patients,” presenter Gregory T. Everson, MD, University of Colorado, Denver, said. “And, in this study, this was achieved despite a high prevalence of genotype 1a subtype, advanced fibrosis, cirrhosis and a predominance of non-CC IL28B genotype. … These results support phase 3 trials with a twice-daily, fixed-dose combination of this regimen at the 75-mg dose of [BMS-791325].”
Disclosure: The researchers report numerous financial disclosures.
For more information:
Everson GT. LB-1: Late-Breaking Abstract Session: Phase 2b Study of the Interferon-free and Ribavirin-free Combination of Daclatasvir, Asunaprevir, and BMS-791325 for 12 Weeks in Treatment-Naive Patients with Chronic HCV Genotype 1 Infection. Presented at: The Liver Meeting 2013; Nov. 1-5, Washington.