In the 631-patient SAPPHIRE-I study, patients new to therapy receiving 12 weeks of 3D regimen achieved a sustained virologic response at 12 weeks post-treatment ( SVR12 ) of 96%. The majority of patients were genotype 1a ( GT1a ), considered the more difficult-to-treat subtype, and the SVR12 rates of GT1a and GT1b were 95% and 98%, respectively. The rate of virologic relapse or breakthrough was low, occurring in 1.7% of patients receiving the 3D regimen. In addition, discontinuation rates due to adverse events were low, and of an equal percentage ( 0.6% ) in both active and placebo groups.
SAPPHIRE-I is a global, multi-center, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of 12 weeks of treatment with ABT-333 ( 250 mg ), Ribavirin ( weight-based ), both dosed twice-daily, and the fixed-dose combination of ABT-450 / Ritonavir ( 150/100 mg ) co-formulated with ABT-267 ( 25 mg ) and dosed once-daily in non-cirrhotic, GT1a and GT1b HCV-infected, treatment-naive adult patients.
The study population consisted of 631 GT1 treatment-naive patients with no evidence of liver cirrhosis, with 473 patients randomized to the 3D regimen plus Ribavirin for 12 weeks, and 158 patients randomized to placebo for the initial 12 weeks. Patients initially randomized to placebo for the first 12 weeks then received open-label treatment with the 3D regimen plus Ribavirin for 12 weeks.
Following 12 weeks of treatment with 3D regimen plus Ribavirin, 96% ( 455/473 ) of patients achieved SVR12 based on intent-to-treat analysis where patients with missing values for any reason were considered treatment failures. In the active treatment arm, patients with GT1b infection achieved 98% SVR12 ( 148/151 ), while patients with GT1a achieved 95% SVR12 ( 307/322 ).
The most commonly reported adverse events in the 3D and placebo arms were fatigue, headache and nausea. Discontinuations due to adverse events were reported in 0.6% of patients receiving the 3D regimen and 0.6% of patients receiving placebo. The rate of virologic relapse or breakthrough was low, occurring in 1.7% of patients receiving the 3D regimen.
The 3D regimen consists of boosted protease inhibitor ABT-450 / Ritonavir, NS5A inhibitor ABT-267, and non-nucleoside polymerase inhibitor ABT-333. 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, 2013