Efficacy and safety of ombitasvir/paritaprevir/r and dasabuvir compared to IFN-containing regimens in genotype 1 HCV patients: The MALACHITE-I/II trials

Background & Aims: Telaprevir plus pegylated interferon/ribavirin (TPV + PegIFN/RBV) remains a therapeutic option for chronic hepatitis C virus (HCV) genotype (GT) 1 infection in many regions. We conducted two open-label, phase IIIb trials comparing safety and efficacy of all-oral ombitasvir/paritaprevir/ritonavir and dasabuvir +/- ribavirin (OBV/PTV/r + DSV +/- RBV) and TPV + PegIFN/RBV. Methods: Treatment-naive (MALACHITE-I) or PegIFN/RBVexperienced (MALACHITE-II) non-cirrhotic, chronic HCV GT1-infected patients were randomized to OBV/PTV/r + DSV + weight-based RBV, OBV/PTV/r + DSV (treatment-naive, GT1b-infected patients only), or 12 weeks of TPV + PegIFN + weight-based RBV and 12-36 additional weeks of PegIFN/RBV. The primary endpoint was sustained virologic response 12 weeks post-treatment (SVR12). Patient-reported outcome questionnaires evaluated mental and physical health during the studies. Results: Three hundred eleven treatment-naive and 148 treatment-experienced patients were randomized and dosed. Among treatment-naive patients, SVR12 rates were 97% (67/69) and 82% (28/34), respectively, in OBV/PTV/r + DSV + RBV and TPV + PegIFN/RBV-treated GT1a-infected patients; SVR12 rates were 99% (83/84), 98% (81/83), and 78% (32/41) in OBV/PTV/r+ DSV + RBV, OBV/PTV/r + DSV, and TPV + PegIFN/RBV-treated GT1b-infected patients. Among treatment-experienced patients, SVR12 rates were 99% (100/101) and 66% (31/47) with OBV/PTV/r + DSV + RBV and TPV + PegIFN/RBV. Mental and physical health were generally better with OBV/PTV/r + DSV +/- RBV than TPV + PegIFN/RBV. Rates of discontinuation due to adverse events (0-1% and 8-11%, respectively, p < 0.05) and rates of hemoglobin decline to < 10 g/dl (0-4% and 34-47%, respectively, p < 0.05) were lower for OBV/PTV/r + DSV +/- RBV than TPV + PegIFN/RBV. Conclusions: Among non-cirrhotic, HCV GT1-infected patients, SVR12 rates were 97-99% with 12 week, multi-targeted OBV/PTV/r + DSV +/- RBV regimens and 66-82% with 24-48 total weeks of TPV + PegIFN/RBV. OBV/PTV/r + DSV +/- RBV was associated with a generally better mental and physical health, more favorable tolerability, and lower rates of treatment discontinuation due to adverse events. (C) 2015 The Authors. Published by Elsevier B.V. on behalf of the European Association for the Study of the Liver.