The first detailed results from pivotal phase III study, PEARL-III, were presented as part of the 21st Conference on Retroviruses and Opportunistic Infections ( CROI ).
PEARL-III evaluated the efficacy and safety of 12 weeks of treatment with AbbVie's investigational therapy with or without Ribavirin in non-cirrhotic, adult patients with chronic genotype 1b ( GT1b ) hepatitis C virus ( HCV ) infection who were new to treatment.
The PEARL-III study met its primary and secondary endpoints. In the 419-patient study, sustained virologic response rates 12 weeks post-treatment ( SVR12 ) of 99.5 and 99.0% were achieved with the AbbVie regimen with and without Ribavirin, respectively. There were no study drug discontinuations due to adverse events.
PEARL-III enrolled patients across different demographics and characteristics. Response rates in patients with certain characteristics ( male gender, Black race and IL28B non-CC genotypes ) were examined, as these patient populations have historically been associated with having a decreased response to treatment. High response rates were observed across all patients in the study, including those with these characteristics.
In PEARL-III study, the population consisted of 419 GT1b treatment-naive patients with no evidence of liver cirrhosis: 209 patients randomized to the regimen without Ribavirin for 12 weeks, and 210 patients randomized to the regimen with Ribavirin for 12 weeks.
Following 12 weeks of treatment, 99.0% receiving the regimen without Ribavirin ( n=207/209 ) and 99.5% receiving the regimen with Ribavirin ( n=209/210 ) achieved SVR12. Patients in the treatment arm without Ribavirin received placebo in substitution for Ribavirin.
Patients with different demographics and characteristics were enrolled in the study, including gender, race ( Black versus non-Black ), Hispanic/Latino ethnicity, age, geographic region, body mass index ( BMI ), liver fibrosis stage, IL28B genotype and viral load.
Across treatment arms in PEARL-III, there were no documented relapses within 12 weeks post-treatment. No on-treatment virologic failures occurred in the treatment arm without Ribavirin and a single virologic failure occurred in the treatment arm with Ribavirin. While all patients in the study completed therapy, two patients in the arm without Ribavirin were lost to follow-up and therefore were considered treatment failures.
The most commonly reported adverse events ( greater than 10% for either arm ) were headache, fatigue, pruritus, nausea and asthenia, with pruritus and nausea occurring at a statistically higher rate in the treatment arm with Ribavirin compared to the arm without Ribavirin. Anemia occurred more commonly among patients in the Ribavirin-containing arm with clinically significant anemia requiring Ribavirin dose reductions occurring in 9% of these patients.
The AbbVie investigational regimen consists of the fixed-dose combination of ABT-450 / Ritonavir ( 150/100mg ) co-formulated with ABT-267 ( Ombitasvir ) ( 25mg ), dosed once daily, and ABT-333 ( Dasabuvir ) ( 250mg ) with or without Ribavirin ( weight-based ), dosed twice daily.
The combination of three different mechanisms of action interrupts the HCV replication process with the goal of optimizing SVR rates across different patient populations. ( Xagena )
Source: Abbvie, 2014