April 5, 2013
Most patients with chronic hepatitis C who had been ineligible for or nonresponsive to interferon-based treatment benefited from dual therapy with daclatasvir and asunaprevir in a recent study.
In an open-label, phase 2a study, researchers administered 24 weeks of dual oral therapy with 60 mg NS5A replication complex inhibitor daclatasvir (DCV) once daily and 200 mg NS3 protease inhibitor asunaprevir (ASV) twice a day to 43 Japanese patients aged 20 to 75 years with chronic HCV genotype 1b. The cohort included 21 null responders and 22 who had been ineligible or intolerant to previous therapy with pegylated interferon-alfa and ribavirin (PegIFN-a/RBV).
Thirty-six participants completed therapy. At 4 weeks, more patients in the intolerant/ineligible group had achieved undetectable HCV RNA levels than null responders, with mean RNA reductions of 5.4 log10 IU/mL among intolerant/ineligible patients and 5.6 log10 IU/mL for null responders. All participants had undetectable HCV RNA levels after 8 weeks. Sustained virologic response (SVR) at 12 and 24 weeks after completion of treatment occurred in 76.7% of the cohort (90.5% of null responders and 63.6% of intolerant/ineligible participants).
Virologic breakthrough occurred in three intolerant/ineligible participants, along with four relapses after treatment. No null responders experienced relapse or virologic breakthrough. Investigators observed no associations between breakthrough or relapse and factors including gender, IL28B genotype, age, HCV RNA level at baseline, fibrosis stage and reasons for previous treatment ineligibility.
Common adverse events, all typically mild, included headache, nasopharyngitis, diarrhea and increases to ALT/AST. Five patients experienced serious events, and three discontinued treatment for hyperbilirubinemia or transaminase elevation.
“Dual oral therapy with daclatasvir and asunaprevir elicited rapid clearance of detectable HCV RNA and achieved high rates of SVR in two difficult-to-treat patient populations,” the researchers concluded. “These results confirm initial findings that HCV genotype 1b infections can be cured with daclatasvir combined with asunaprevir, without PegIFN-a/RBV.
“Further research will assess the benefits of this and other [direct-acting antiviral] combinations in larger and more diverse patient populations.”
Disclosure: See the study for a full list of relevant disclosures.