CARE Liver Disease Faculty Canadian Perspectives from EASL 2013
Abstract 1416: Faldaprevir Plus Pegylated Interferon Alfa-2A and Ribavirin in Chronic HCV Genotype-1 Treatment-Naïve Patients: Final Results From STARTVerso1, a Randomised, Double-Blind, Placebo-Controlled Phase III Trial
Background: Faldaprevir (FDV) is a once-daily (QD) NS3/4A protease inhibitor. This double-blind, placebo-controlled Phase III study (STARTVerso1) assessed the efficacy and safety of FDV plus pegylated interferon alfa-2a and ribavirin (PegIFN/RBV).
Methods: Treatment-naïve patients with chronic HCV genotype-1 (GT-1) infection were randomised 1:2:2 to receive 24 weeks' PegIFN/RBV with: placebo for 24 weeks (arm 1); FDV 120 mg QD for 12 or 24 weeks (response guided; arm 2); or FDV 240 mg QD for 12 weeks (arm 3). Patients with early treatment success (ETS, HCV RNA < 25 IU/mL at week 4 and undetectable at week 8) in arms 2 and 3 stopped all treatment at week 24. Patients without ETS and those in arm 1 received PegIFN/RBV for 48 weeks. Randomisation was stratified by HCV GT-1 subtype and race. The primary endpoint was sustained virological response 12 weeks after planned end of treatment (SVR12).
Results: 652 patients were treated: mean age 48 years, 52% male, 78% Caucasian, 20% Asian, 17% Grade ≥3 fibrosis, 39% IL28B CC, 66% GT-1b.
All study medications were discontinued due to adverse events (AEs) in 4%, 4% and 5% of patients, and FDV only was discontinued in 0%, 1% and 3% of patients, respectively. Serious AEs occurred in 6%, 7% and 7% of patients. Grade 3 rash occurred in < 1% of patients in each arm; no patients had Grade 4 rash. Up to week 24, haemoglobin ≤8.5 g/dL occurred in 2%, 3% and 3% of patients, respectively.
Conclusions/Key Take Away: FDV plus PegIFN/RBV significantly increased SVR12 rates in HCV GT-1 patients in Europe and Japan compared with PegIFN/RBV alone and was well tolerated. In total, 88% of patients treated with FDV were eligible to stop all treatment at week 24.
Triple therapy including boceprevir or telaprevir has markedly improved SVR rates (63-75%)REF compared with PegIFN/RBV (40–50%) in patients with HCV GT-1. However, challenges remain including adverse effects (e.g., rash, anemia), the need for prolonged therapy in ~50% of patients, and multiple daily dosing schedules. Data from the STARTVerso1 trial of the second generation protease inhibitor, faldaprevir, are encouraging as it demonstrates excellent efficacy of this once daily medication (SVR ~80%), limited toxicity, and the ability to treat nearly 90% of patients for only 24 weeks.