US drug maker AbbVie has completed its phase 3 clinical programme and released results of four additional studies designed to evaluate its investigational all-oral, interferon-free therapy with and without ribavirin (RBV) in patients with chronic genotype 1 (GT1) hepatitis C virus (HCV) infection.
The results are from the PEARL-II, PEARL-III, PEARL-IV and TURQUOISE-II studies, which are part of the six phase 3 registrational studies being carried out by AbbVie to treat genotype 1 (GT1) hepatitis C virus (HCV) infection using a regimen containing Enanta Pharmaceuticals’ lead protease inhibitor ABT-450.
Around 2,308 patients from more than 25 countries around the world have participated in the six phase 3 trials.
According to the company, the results of these studies show high sustained virologic response rates 12 weeks post-treatment (SVR12) and tolerability in the GT1 patients.
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.
The studies were carried out with and without ribavirin, while the combination of the three different mechanisms of action in this regimen interrupts the HCV replication process with the goal of optimising SVR rates across different patient populations.
The PEARL-II study is designed to assess 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.
A total of 179 GT1b treatment-experienced patients with no evidence of liver cirrhosis were included in the trial, of which 91 were randomised to the regimen without ribavirin for 12 weeks, and 88 were randomised 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.
The PEARL-III study included a total of 419 GT1b treatment-naïve patients with no evidence of liver cirrhosis, out of which 209 were randomised to the regimen without ribavirin for 12 weeks, and 210 were randomised to the regimen plus ribavirin for 12 weeks.
After 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.
PEARL-IV is a global, multi-centre, randomised, double-blind, placebo-controlled study to evaluate 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.
A total of 305 GT1a treatment-naive patients with no evidence of liver cirrhosis were included in the PEARL-IV study, of which 205 patients were randomised to the regimen without ribavirin for 12 weeks, and 100 patients randomised 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 3 study completed in GT1 cirrhotic patients investigating an all-oral, interferon-free regimen.
The trial 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: 208 patients randomised to the regimen with ribavirin for 12 weeks and 172 patients randomised to the regimen with ribavirin for 24 weeks.
After the 12-week treatment, 92% of patients (n=191/208) achieved SVR12 and following 24 weeks of treatment, 96% of patients (n=165/172) achieved SVR12.
Most commonly reported adverse events in PEARL-II and PEARL-III studies were fatigue and headache, while fatigue, headache and nausea were the most commonly reported adverse events in PEARL-IV and TURQUOISE-II trials.
ABT-450, which was discovered during the ongoing collaboration between AbbVie and Enanta Pharmaceuticals for HCV protease inhibitors and regimens, is currently being developed by AbbVie for use in combination with AbbVie’s other investigational medicines for the treatment of HCV.
AbbVie, which previously secured breakthrough therapy designation from the US FDA for its regimen with and without ribavirin for HCV GT1, is now on track to start major regulatory submissions early in the second quarter of 2014.
Image: Globally, approximately 160 million people are chronically infected with hepatitis C. Photo: courtesy of freedigitalphotos.net.