Daclatasvir + Asunaprevir Works Well for Patients Who Cannot Use Interferon

A dual combination of the HCV NS5A inhibitor daclatasvir (formerly BMS-790052) and HCV protease inhibitor asunaprevir (formerly BMS-650032) cured three-quarters of Japanese patients unable to take interferon, including 90% of prior null responders, according to a study described in the April 2013 Journal of Hepatology.

The advent of direct-acting antiviral agents that attack hepatitis C virus (HCV) has brought about a new treatment paradigm. Most new drugs have been initially tested as an addition to interferon-based therapy, but many people cannot use interferon either due to intolerance or because it does not work for them.

Yoshiyuki Suzuki from Toranomon Hospital in Tokyo and colleagues conducted an open-label Phase 2a study to evaluate 2 oral direct-acting agents -- 60 mg once-daily daclatasvir plus 200 mg twice-daily asunaprevir taken for 24 weeks -- for people who could not take or were unlikely to benefit from standard interferon/ribavirin treatment.

The analysis included 43 patients, all with HCV genotype 1b (the predominant subtype in Japan). Half were prior null responders to a previous course of interferon -- meaning they showed little or no viral decline -- while the rest could not tolerate or were ineligible to use interferon/ribavirin.

Results

• By week 8 of dual therapy, all participants -- both null responders and those who were interferon intolerant or ineligible -- had undetectable HCV RNA.
• 76.7% of patients overall achieved sustained virological response (SRV), or continued undetectable HCV at both 12 and 24 weeks after completing treatment:
• 90.5% for prior null responders;
• 63.6% for interferon-intolerant or ineligible patients.
• 3 intolerant/ineligible participants experienced viral breakthrough and 4 experienced post-treatment relapse, neither of which occurred in any prior null responders.
• Viral breakthrough and relapse were not significantly associated with predictive factors including IL28B gene pattern, baseline viral load, fibrosis stage, or reason for ineligibility.
• Treatment was general safe and well-tolerated, with mostly mild adverse events including headache, nasopharyngitis (nose or throat inflammation), and diarrhea.
• 5 people experienced serious adverse events, and 3 discontinued therapy for this reason (elevated bilirubin or ALT/AST).

Based on these findings, the researchers concluded, "Dual Therapy with daclatasvir and asunaprevir, without peginterferon/ribavirin, was well tolerated and achieved high SVR rates in 2 groups of difficult-to-treat patients with hepatitis C virus genotype 1b infection."

This combination may not work as well for a more diverse patient population with a higher proportion of people with HCV subtype 1a, which does not respond as well as 1b to many direct-acting agents.

4/24/13

Reference

Y Suzuki, K Ikeda, F Suzuki, et al.Dual oral therapy with daclatasvir and asunaprevir for patients with HCV genotype 1b infection and limited treatment options. Journal of Hepatology58(4):655-662. April 2013.