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

Background & AimsTelaprevir 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.MethodsTreatment-naïve (MALACHITE-I) or PegIFN/RBV-experienced (MALACHITE-II) non-cirrhotic, chronic HCV GT1-infected patients were randomized to OBV/PTV/r + DSV + weight-based RBV, OBV/PTV/r + DSV (treatment-naïve, 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.ResultsThree hundred eleven treatment-naïve and 148 treatment-experienced patients were randomized and dosed. Among treatment-naïve 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.ConclusionsAmong 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.