Regulatory Decision Summary for HOLKIRA PAK

Health Canada considers that the benefit/risk profile of Holkira Pak is favorable when used for the treatment of HCV infection with genotype 1b in adult patients with compensated cirrhosis, who are treatment-naïve or those previously treated with peginterferon/ribavirin.

Holkira Pak is an all-oral regimen comprised of four medications: ombitasvir, paritaprevir, ritonavir, and dasabuvir. Study M14-490 (TURQUOISE III), a Phase IIIb, open-label, multicenter study evaluating the safety and efficacy of Holkira Pak administered for 12 weeks in HCV genotype 1b infected treatment-naïve and treatment-experienced adult patients with compensated cirrhosis, was provided in support of the treatment regimen. The primary efficacy endpoint of sustained virologic response at 12 weeks after completing treatment (SVR12) was achieved by 60/60 (100%) subjects, with a 95% CI of 94.0% to 100.0%. No subject demonstrated on-treatment virologic failure or post-treatment relapse.

Holkira Pak administered for 12 weeks in HCV genotype 1b infected patients with compensated cirrhosis was generally well tolerated with no subjects prematurely discontinuing study drug because of a treatment-emergent serious adverse event. The majority of subjects (76.7%) experienced 1 or more treatment-emergent adverse events during the treatment period, and most were mild or moderate in severity. The overall incidence of treatment-emergent serious adverse events (1.7%) was low. There were no treatment-emergent serious adverse events that led to premature discontinuation of study drug. No deaths were reported.

Treatment-emergent adverse events reported for ≥10.0% of subjects were fatigue, diarrhea, headache, arthralgia, dizziness, insomnia, and pruritus. Clinically significant lab abnormalities were infrequent and occurred at a lower frequency than previously observed among genotype 1 cirrhotic patients who received Holkira Pak with ribavirin for the same 12-week duration.

Based on the data submitted, Health Canada considers that the anticipated benefits of Holkira Pak outweigh the potential risks for the proposed dosing without ribavirin administered for 12 weeks in patients infected with chronic HCV genotype 1b with compensated cirrhosis.