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Quadruple Therapy Yields High SVR Rates in Patients with HCV

In the MATTERHORN clinical trial, prior partial and null responders treated with a regimen of danoprevir/ritonavir, mericitabine plus pegylated interferon alfa-2a/ribavirin achieved a sustained virologic response after 24 weeks of treatment.

“The present study was designed with the primary objective of evaluating the efficacy and safety of various [interferon-free] and [interferon-based] combination regimens with [danoprevir and ritonavir] and mericitabine in [hepatitis C virus] genotype 1 patients who had not responded to prior treatment with [PEG-IFN-a and ribavirin],” the researchers wrote. 

Jordan J. Feld

Researchers, including HCV Next Editorial Board member Jordan J. Feld, MD, MPH, of the Toronto Center for Liver Disease, randomly assigned 152 prior partial responders to an interferon-free (IFN-free) regimen of danoprevir/ritonavir at 100 mg/100 mg with 1,000 mg mericitabine with ribavirin; triple therapy with danoprevir/ritonavir plus PEG-IFN a-2a and ribavirin; or quadruple therapy with danoprevir/ritonavir with mericitabine and PEG-IFN a-2a and ribavirin twice a day for 24 weeks. In addition, 229 prior null responders were randomly assigned to quadruple therapy with danoprevir/ritonavir with mericitabine and PEG-IFN a-2a/ribavirin alone for 24 weeks or the same regimen for 24 weeks plus an additional 24 weeks of PEG-IFN a-2a/ribavirin.

Overall, 46.2% of prior partial responders in the IFN-free group achieved an SVR at 24 weeks, as well as 51% in the triple therapy group and 86% in the quadruple therapy group. In prior null responders, 45.5% in the IFN-free group achieved SVR at 24 weeks, as well as 80.5% in the triple therapy group and 83.8% in the quadruple therapy group.

Prior partial responders with HCV genotype 1a and genotype 1b achieved SVR24 rates of 75% and 96.2%, respectively, after quadruple therapy, and prior null responders achieved SVR 24 rates of 68.1% and 100%, respectively, after quadruple therapy.

Eighteen patients with genotype 1a and seven patients with genotype 1b infection experienced viral breakthrough during treatment with danoprevir/ritonavir. In addition, 10 patients with genotype 1a and one patient with genotype 1b infection who received PEG-IFN a-2a/ribavirin experienced viral breakthrough.

Overall, 54 patients with genotype 1a and 24 with genotype 1b infection relapsed. Eight patients withdrew from the trial due to adverse events. No deaths were reported. However, 18 patients reported serious adverse events during treatment. The most common adverse events were fatigue, headache, pyrexia and myalgia, all typical with treatment with PEG-IFN a-2a/ribavirin, according to the research.    

“The results of this study demonstrate that the quadruple combination of danoprevir/[ritonavir], mericitabine and PEG-IFN a-2a/ribavirin is well tolerated and produces high overall SVR rates in patients with a prior partial or prior null response to PEG-IFN-a/ribavirin,” the researchers concluded.

Disclosure: The research was funded by F. Hoffmann-La Roche. Feld reports consulting for AbbVie, Bristol-Myers Squibb, Gilead, Janssen and Merck, as well as participating in research for AbbVie, Boehringer Ingelheim, Gilead, Merck, Roche and Santaris. See the study for other researchers’ relevant financial disclosures.