Enanta declare results from phase 3 CERTAIN-1 study of genotype 1 chronic HCV infected Japanese patients
Enanta Pharmaceuticals, Inc., a research and development-focused biotechnology company, announced results from AbbVie’s phase 3 CERTAIN-1 study of 8 weeks of treatment with AbbVie’s investigational, pan-genotypic, ribavirin (RBV)-free regimen of glecaprevir (ABT-493)/pibrentasvir (ABT-530) (G/P) in Japanese patients with genotype 1 (GT1) chronic hepatitis C virus (HCV) infection without cirrhosis. Top-line results from the study demonstrated 99 per cent (n=105/106) of patients without cirrhosis, who represent the majority of HCV patients, and without the Y93H variant, achieved sustained virologic response at 12 weeks after treatment (SVR12). The one patient who did not reach SVR12 in this intent to treat (ITT) population was lost to follow-up. All 23 patients with the Y93H variant were assigned to the G/P arm of this comparator study, and 100% achieved SVR12.
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These data are the first to be released by AbbVie from registrational studies in Japan as part of its global G/P clinical development programme, designed to investigate a faster path to virologic cure for all major HCV genotypes and with the goal of addressing treatment areas of continued unmet need. The results demonstrated from the CERTAIN-1 study are consistent with recently announced 8-week, GT1 data from AbbVie’s global registration studies of G/P.
Approximately 1 million people are living with hepatitis C in Japan, with 60 to 70 percent of those infected with GT1 chronic HCV.1,3 Patients participating in the CERTAIN-1 study were further representative of the HCV-infected patient population in Japan, where the prevalence of HCV infection increases with age, because a majority of patients in the study were over 65 years of age.4
The CERTAIN-1 study compared the safety and efficacy of 8 weeks of treatment with the investigational G/P regimen to 12 weeks of treatment with ombitasvir/paritaprevir/ritonavir (OBV/PTV/r), in GT1 chronic HCV-infected patients. The primary endpoint of the study was met, as 8 weeks of G/P was shown to be non-inferior to 12 weeks of OBV/PTV/r (100 percent SVR12; n=52).
Additionally, in sub-study 1 evaluating GT1 patients (treated with G/P) without cirrhosis and who were new to treatment with direct-acting antivirals (DAA), no patients discontinued treatment due to adverse events (AEs). In patients treated with OBV/PTV/r, there was one who discontinued treatment due to AEs. In patients receiving the G/P regimen, the most common AEs, occurring at a rate greater than 5 per cent, were nasopharyngitis (inflammation of the throat and nasal passages) and pruritus (itchiness).
The CERTAIN-1 study is a phase 3, multicenter study evaluating the efficacy, safety and pharmacokinetics (PK) of G/P in Japanese adults. Sub-study 1 is a randomized, open-label and active-controlled study in genotype 1 (GT1) chronic HCV-infected patients without cirrhosis who are new to DAA treatment. Patients who tested negative for the Y93H resistance associated variant received either 8 weeks of G/P or 12 weeks of OBV/PTV/r (2:1 randomization ratio). All Y93H positive patients were assigned to receive 8 weeks of G/P and all (n=23/23) achieved SVR12. The primary objectives were safety and non-inferiority of G/P compared to OBV/PTV/r. Sub-study 2 is a non-randomized, open-label study evaluating GT1-6 HCV patients with specific treatment challenges, including those with compensated cirrhosis (Child-Pugh A), chronic kidney disease (CKD) and those who were not cured with previous DAA treatment.
AbbVie’s glecaprevir/pibrentasvir (G/P) clinical development program was designed to investigate a faster path to virologic cure for all major HCV genotypes (GT1-6) and with the goal of addressing treatment areas of continued unmet need. In Japan, AbbVie studied the G/P regimen in additional dedicated clinical trials due to patient and viral characteristics specific to the Japanese HCV patient population.
G/P is an investigational, once-daily regimen that combines two distinct antiviral agents in a fixed-dose combination of glecaprevir (300mg), an NS3/4A protease inhibitor, and pibrentasvir (120mg), an NS5A inhibitor. G/P is dosed once-daily as three oral tablets. Glecaprevir is Enanta’s second protease inhibitor being developed through its collaboration with AbbVie and is one of the two new direct-acting antivirals in G/P. G/P is an investigational product and its safety and efficacy have not been established in Japan