Safety of ABT-450/r/Ombitasvir + Dasabuvir With or Without Ribavirin in HCV Genotype 1-infected Patients, by Baseline Demographics
Background: ABT-450 is an HCV NS3/4A protease inhibitor dosed with ritonavir (r) 100mg, identified by AbbVie and Enanta. Ombitasvir (formerly ABT-267) is an NS5A inhibitor, and dasabuvir (formerly ABT-333) is an NS5B RNA polymerase inhibitor. The randomized phase 3 PEARL trials evaluated the safety and efficacy of the “3D” regimen of ABT-450/ritonavir/ombitasvir and dasabuvir with or without ribavirin (RBV) in HCV genotype 1-infected patients. SVR12 rates >90% were achieved in all treatment arms. Safety outcomes in these trials according to baseline demographics are reported.
Methods: Non-cirrhotic HCV GT1b treatment-experienced (PEARL II) and treatment-naive (PEARL III) patients, and non-cirrhotic HCV GT1a treatment-naive patients (PEARL IV) were randomized to co-formulated ABT-450/r/ombitasvir (150mg/100mg/25mg QD) + dasabuvir (250mg BID) with RBV or placebo/no RBV. The percentage of patients experiencing any treatment-emergent adverse event (AE), severe AE, serious AE, and AE leading to treatment discontinuation was determined according to sex, age, race, ethnicity, and history of diabetes. Homogeneity of treatment effect across subgroups for each event type was assessed using the Breslow-Day test.
Results: A total of 910 patients received at least one dose of study treatment in the PEARL-II (n=186), PEARL-III (n=419), and PEARL-IV (n=305) trials. Most patients experienced at least 1 AE, but the majority of events were mild. There were no statistically significant differences in event rates according to the categories analyzed (Table). AEs occurring in >20% of patients in both the 3D+RBV and 3D groups were fatigue (29.9% and 26.5%) and headache (24.4% and 25.3%). Overall, 4 patients (0.4%, 2 in each treatment group) discontinued due to AEs (3D+RBV arm: 1 patient with anxiety, dyspnea, pyrexia and tachycardia, and 1 with pancreatitis that started prior to dosing; 3D arm: 1 patient with diverticulitis and 1 patient with drug abuse).
Conclusion: The 3D regimen of ABT-450/r/ombitasvir + dasabuvir with or without RBV was well tolerated in non-cirrhotic HCV GT1-infected patients, with low rates of discontinuation. The AE profile of the regimen was similar with and without RBV regardless of age, gender, race, ethnicity, or history of diabetes.
Abbvie, Merck, Gilead, Janssen, BMS: Investigator, Research support
Gilead, Merck, Janssen: Speaker's Bureau, Speaker honorarium
Janssen, BMS, Gilead: Scientific Advisor, Consulting fee
Abbvie, Boerhinger-Ingelheim, BMS, Gilead, Janssen, Merck, Hyperion, Intercept, Sundise: Scientific Advisor, Consulting fee
H. Van Vlierberghe, Gilead, Merck, Novartis, Asttellas, Janssen, Roche: Research Contractor, Research support
Roche, Merck, AbbVie, BMS: Scientific Advisor, Consulting fee
D. Wyles, AbbVie, BMS, Gilead, Merck, Vertex Pharmaceuticals: Research Contractor, Research support
AbbVie, BMS, Gilead, Janssen: Scientific Advisor, Consulting fee
M. Brunetto, AbbVie, BMS, Gilead, Janssen, MSD, Roche, Novartis: Speaker's Bureau, Speaker honorarium
W. Xie, AbbVie Inc.: Employee and Shareholder, Salary
D. Cohen, AbbVie Inc.: Employee and Shareholder, Salary
Y. Luo, AbbVie Inc.: Employee and Shareholder, Salary
J. Enejosa, AbbVie Inc.: Employee and Shareholder, Salary