Data from the PEARL-I trial of patients with hepatitis C genotype 4 show high rates of sustained virologic response at 12 weeks associated with combination treatment with ABT-450 (a protease inhibitor boosted by ritonavir) and ombitasvir.
Christophe Hezode, MD, began his address on Friday at the general session of the 2014 EASL International Liver Conference in London by drawing attention to the increasing prevalence of the HCV genotype 4 (HCV-G4) in the Middle East and sub-Saharan Africa.
“HCV-G4 now accounts for almost 90% of HCV infections in Egypt. Its prevalence has increased in several European countries and treatment with peginterferon/ritonavir (pegIFN/RBV) therapy of HVC-GT4 results in SVR rates of only 50%-79% and associated with significant toxicity,” he said.
Hezode presented results from the phase 2 PEARL-I study, which looked at an interferon-free regimen of ABT-450 with ritonavir plus ombitasvir (formerly ABT-267) with or without ritonavir in HCV-GT4 cirrhotic and non-cirrhotic patients. ABT-450 is a potent NS3/4A protease inhibitor (identified by AbbVie and Enanta) which, when combined with ritonavir, increases the overall exposure of ABT-450 in HCV patients. Ombitasvir is a potent NS5A inhibitor. Both agents have shown potent antiviral activity in vitro against HCV-G1-6.
The PEARL-1 global phase 2b study (being conducted at 47 sites in 8 countries) involves 2 sub-study groups: sub-study group 1 has 6 treatment arms of patients with no cirrhosis; sub-study group 2 has only 2 treatment arms of patients with compensated cirrhosis. Investigators plan on including approximately 40 patients in each treatment arm.
Hezode presented results for 3 treatment arms of subgroup 1, comparing the safety and efficacy of 3 three trial arms involving a total of 135 patients who received one of the following 12-week combination therapy regimens:
In the study, “all interferon-free 12-week regimens of ABT-450/ritonavir plus ombitasvir resulted in sustained virologic response rates at 12 weeks (SVR12) of 90% or higher in treatment-naïve HVC GT4 patients,” Hezode said.
The ABT-450/ritonavir plus ombitasvir SVR12 rate was 90.9%. The ABT-450/ritonavir plus ombitasvir/ribavirin SVR12 was 100%.
The sustained virologic response at 4 weeks (SVR4) rate “was 100% in treatment-experienced patients receiving ABT-450/ritonavir plus ombitasvir/ribavirin,” Hezode said. “The 12-week regimens of ABT-450/ritonavir plus ombitasvir/ribavirin were generally well-tolerated. No patients discontinued or interrupted the study because of adverse events and a fall in haemoglobin to less than 10 g/dl was observed in only a few patients.”
Kamal SM, Nasser, IA, Hepatitis C genotype 4: What we know and what we don’t yet know. Hepatology 2008 47(4): 1371-83.