BOSTON — Patients with HCV genotype 1 achieved sustained virologic response to triple therapy with asunaprevir, daclatasvir and BMS-791325, according to data presented at a late-breaking session at The Liver Meeting.
In the first of a two-part, open-label study, researchers randomly administered 200 mg NS3 protease inhibitor asunaprevir (ASV) twice daily, 60 mg NS5A replication complex inhibitor daclatasvir (DCV) four times a day and 75 mg non-nucleoside NS5B polymerase inhibitor BMS-791325 twice daily for either 24 (n=16) or 12 weeks (n=16) to treatment-naive, noncirrhotic patients with chronic HCV genotype 1. The cohort had a mean baseline HCV RNA level of 6.26 log10 IU/mL; 75% of participants had HCV genotype 1A and 72% had a non-CC IL28B genotype.
“In this phase 2a study of triple direct-acting antiviral therapy, we sought to enhance virological responses, because dual regimen is not as effective against genotype 1a infection,” researcher Gregory T. Everson, MD, of Colorado, said. “We wanted to improve the efficacy in genotype 1a infection, maintain tolerability, and of course, if possible, shorten treatment duration to 12 weeks.”
All participants in both arms had HCV RNA levels below the lower limit of quantification (LLOQ, 25 IU/mL) after 4 weeks of treatment. By week 12 of treatment, 94% of the 24-week and 88% of the 12-week groups had maintained RNA levels below LLOQ. SVR4 was achieved by 94% of participants in the 24-week group, and SVR12 was met by 94% of the 12-week group. Among patients with genotype 1A specifically, 92% in the 24-week group and 100% in the 12-week group had RNA levels below LLOQ at 4 weeks after treatment. No incidence of relapse or virologic breakthrough occurred among any participants.
Commonly reported adverse events included headache (30% of patients), diarrhea (25%) and asthenia (16%). Three serious events occurred, including renal calculus, headache and lymphopenia, but none was considered treatment related. No participants discontinued the study because of adverse events, and no increases of grade 3 or 4 to ALT, AST or bilirubin occurred.
“This interferon-free and ribavirin-free triple direct-acting antiviral combination … resulted in high rates of SVR after both 12 and 24 weeks of treatment,” Everson said. “SVR4 was achieved in all treatment-naive genotype 1 patients with post-treatment data available, including harder-to-treat patients with genotype 1A infection, high viral load and non-CC IL28B genotype.
“Some of these patients have been followed up to 24 weeks; with available data today, we have not yet seen relapse. Further investigation … is warranted.”
The second part of the study, which had been delayed until data had been acquired from the first part, had been fully enrolled upon the researchers’ presentation, and will consist of patients randomly assigned for 24 or 12 weeks to the same treatment, with the exception of a larger dose of BMS-791325 (150 mg twice daily).
Disclosure: The researchers reported numerous financial disclosures.
For more information:
Everson GT. LB3: An Interferon-free, Ribavirin-free 12-week Regimen of Daclatasvir (DCV), Asunaprevir (ASV) and BMS-791325 Yielded SVR4 of 94% in Treatment-Naive Patients with Genotype (GT) 1 Chronic Hepatitis C Virus (HCV) Infection. Presented at: The Liver Meeting 2012; Nov. 9-13, .