Results From the Phase 2 PEARL-I Study: Interferon-Free Regimens of ABT-450/r + ABT-267 With or Without Ribavirin in Patients With HCV Genotype 4 Infection (2014)

Introduction: ABT-450 is an HCV protease inhibitor (dosed with ritonavir 100 mg, ABT-450/r) identified by AbbVie and Enanta; ABT-267 is an NS5A inhibitor. Both compounds have shown potent antiviral activity in vitro against HCV genotypes (GTs) 1-4 and 6. HCV GT4 is common in the Middle East and sub-Saharan Africa, and accounts for almost 90% of HCV infections in Egypt. HCV GT4 prevalence has increased in several European countries. Here, we report safety and efficacy results from the PEARL-I study for non-cirrhotic HCV GT4-infected patients receiving ABT-450/r+ABT-267 ± ribavirin (RBV). Methods: Treatment-naïve and peginterferon/RBV-experienced patients with chronic HCV GT4 infection were enrolled. Treatment-naïve patients received ABT-450/r (150/100 mg once per day) + ABT-267 (25 mg once per day) ± weight-based RBV for 12 weeks. Experienced patients received the RBV-containing regimen for 12 weeks. Rates of RVR (HCV RNA<25 IU/mL at week 4) and EOTR (HCV RNA<25 IU/mL at week 12) in treatment-naïve patients are reported. SVR12 rates for treatment-naïve patients and SVR4 rates for experienced patients will be presented. Results: Forty-four treatment-naïve patients received the RBV-free regimen and 42 treatment-naïve patients received the RBV-containing regimen. Baseline characteristics and efficacy results are in the table. Among treatment-naïve patients, there were no serious adverse events (AEs) or AEs leading to discontinuation or interruption of study drug. The most frequent treatment-emergent AEs were headache and asthenia. One patient receiving the RBV-free regimen had an asymptomatic grade 3 elevation in AST at a single visit. This elevation resolved with continued dosing. Conclusion: Interferon-free regimens of ABT-450/r+ABT-267±RBV achieved high RVR and EOTR rates in HCV GT4-infected, treatment-naïve patients. This research was funded by AbbVie. AbbVie participated in the design of the study, the interpretation of data, review, and approval of the abstract. Christine Ratajczak (AbbVie) provided medical writing services. Disclosure - C Hezode - Speaker’s Bureau/Advisor: Abbvie, Bristol-Myers Squibb, Gilead sciences, Janssen, Merck, Roche. P Marcellin - Consultant: Roche, Gilead, BMS, Vertex, Novartis, Janssen-Tibotec, MSD, Boehringer, Abbott, Pfizer; Grant/Research Support: Roche, Gilead, BMS, Janssen-Tibotec, MSD, Novartis; Speaker’s Bureau and Teaching: Roche, Gilead, BMS, Vertex, Janssen-Tibotec, MSD, Abbott; Novartis. S Pol - Board Membership: Sanofi, Bristol-Myers-Squibb, Boehringer Ingelheim, Tibotec Janssen Cilag, Vertex, Gilead, Roche, MSD, Novartis, Abbvie; Speaker’s Bureau and Teaching: Glaxo Smith Kline. T Hassanein - Grant/Research Support: AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb, Eisai, Gilead Sciences, Janssen, Idenix, Ikaria, Mochida, Roche, Ocera, Taigen, Takeda, Salix, Sundise, Vertex. Speaker’s Bureau: Baxter, Bristol-Myers Squibb, Gilead, Salix; Advisory Board: AbbVie, Bristol-Myers Squibb. K Fleischer Stepniewska - Speaker’s Bureau for: Bristol-Myers Squibb, Gilead Sciences, Tibotec Janssen Cilag, MSD, and Roche; Grant/Research Support from AbbVie. Investigator in Abbvie clinical trial. EMC Instytut Medyczny Spolka Akcyjna, Wroclaw, Poland and Medical University of Wroclaw, Poland. T Baykal - Employee/Stockholder: AbbVie. T Wang - Employee/Stockholder: AbbVie. S Lovell - Employee/Stockholder: AbbVie. T Pilot-Matias - Employee/Stockholder: AbbVie. R Vilchez - Employee/Stockholder: AbbVie. This research was supported by an industry grant from AbbVie.Table 1: Baseline characteristics and efficacy results