AbbVie has completed its Phase III clinical trial program and released results of four additional studies designed to assess its investigational all-oral, interferon-free therapy with and without ribavirin (RBV) in patients with chronic genotype 1 (GT1) hepatitis C virus (HCV) infection.
Results are of the PEARL-II, PEARL-III, PEARL-IV and TURQUOISE-II studies, which are part of the six Phase III registrational studies being conducted by AbbVie to treat genotype 1 (GT1) hepatitis C virus (HCV) infection using a regimen containing Enanta Pharmaceuticals’ lead protease inhibitor ABT-450.
ABT-450 is part of AbbVie’s investigational three direct-acting antiviral regimen that consists of the fixed-dose combination of ABT-450/ritonavir (150/100mg) co-formulated with ABT-267 (25mg), dosed once daily, and ABT-333 (250mg) with or without ribavirin (weight-based), dosed twice daily.
A total of 2,308 patients from over 25 countries around the world have participated in the six Phase III trials.
The company said that the results of these studies demonstrate high sustained virologic response rates 12 weeks post treatment (SVR12) and tolerability in the GT1 patients.
PEARL-II study is designed to evaluate the efficacy and safety of 12 weeks of treatment with the three direct-acting antiviral regimen with and without ribavirin in non-cirrhotic, GT1b HCV-infected, treatment-experienced adult patients.
About 179 GT1b treatment-experienced patients with no evidence of liver cirrhosis have participated in the trial, of which 91 were randomized to the regimen without ribavirin for 12 weeks, and 88 were randomized to the regimen plus ribavirin for 12 weeks.
In the ribavirin-free arm, 100% (n=91/91) of patients achieved SVR12, while 97% (n=85/88) achieved SVR12 in the ribavirin-containing arm.
A total of 419 GT1b treatment-naïve patients with no evidence of liver cirrhosis were enrolled in the PEARL-III study, out of which 209 were randomized to the regimen without ribavirin for 12 weeks, and 210 were randomized to the regimen plus ribavirin for 12 weeks.
Following 12 weeks of treatment, 99% of patients receiving the regimen without ribavirin (n=207/209) and 99% of them receiving the regimen plus ribavirin (n=209/210) achieved SVR12.
The PEARL-IV is a global, multi-center, randomized, double-blind, placebo-controlled study designed to assess the efficacy and safety of 12 weeks of treatment with AbbVie’s regimen with and without ribavirin in non-cirrhotic, GT1a HCV-infected, treatment-naive adult patients.
Around 305 GT1a treatment-naive patients with no evidence of liver cirrhosis were included in the PEARL-IV study, of which 205 patients were randomized to the regimen without ribavirin for 12 weeks, and 100 patients randomized to the regimen with ribavirin for 12 weeks.
After 12 weeks of treatment, 90% of patients receiving the regimen without ribavirin (n=185/205) and 97% receiving the regimen with ribavirin (n=97/100) achieved SVR12.
TURQUOISE-II is the first Phase III study completed in GT1 cirrhotic patients investigating an all-oral, interferon-free regimen, which evaluated the efficacy and safety of 12 or 24 weeks of treatment with AbbVie’s regimen with ribavirin in cirrhotic, GT1a and GT1b HCV-infected, treatment-naive and treatment-experienced adult patients.
The study included 380 GT1a and GT1b, treatment-naive and treatment-experienced patients with compensated cirrhosis of which 208 patients randomized to the regimen with ribavirin for 12 weeks, and 172 patients randomized to the regimen with ribavirin for 24 weeks.
Following 12 weeks of treatment, 92% of patients (n=191/208) achieved SVR12 and following 24 weeks of treatment, 96% of patients (n=165/172) achieved SVR12.
The most commonly reported adverse events in PEARL-II and PEARL-III studies were fatigue and headache, while in PEARL-IV and TURQUOISE-II trials are fatigue, headache and nausea.