- 1University of Pennsylvania, Philadelphia, United States.
- 2Beth Israel Deaconess Medical Center, Boston, MA, United States.
- 3Scripps Clinic, La Jolla, United States.
- 4Tulane Medical Center.
- 5University of Miami, Miami, United States.
- 6Inova Fairfax Hospital.
- 7Conatus Pharmaceuticals.
Background: Despite achieving sustained virologic response (SVR) to HCV therapy there remains a population of HCV patients post liver transplantation with advanced fibrosis or cirrhosis. Emricasan is an orally active, pan-caspase inhibitor which suppresses apoptosis and inflammation and therefore potentially decreases inflammation and fibrosis.
Aim: To determine the safety and efficacy of emricasan in reducing or preventing progression of hepatic fibrosis in post-transplant HCV recipients achieving SVR with anti-viral therapy, and assess changes from baseline in ALT and caspases 3/7.
Methods and patients: Study IDN-6556-07 was a double-blind, randomized, placebo-controlled, multicenter study in liver transplant recipients with chronic HCV who had SVR but had residual HCV-related liver fibrosis or cirrhosis. Sixty-four subjects were randomized to receive 25 mg twice daily of emricasan or placebo in a 2:1 ratio for 24 months.
Results: 41 emricasan and 23 placebo subjects were randomized and 32 emricasan (78.0%) and 19 placebo (82.6%) subjects completed the study. There was no difference in the primary endpoint (Ishak F2-F5, improvement in fibrosis or stability; Ishak F6, improvement) between the emricasan (77.1%) and placebo groups (74.1%). Overall, there was no difference between the emricasan (54.5%) and placebo (60.7%) arms in the rate of fibrosis improvement alone. However, those in the pre-specified F3-5 subgroup had higher rates of stability or improvement in fibrosis in the emricasan group (95.2%) compared to placebo (54.6%);(P=0.01). ALT improved over the first 12 months of therapy with emricasan.
Conclusion: In liver transplant recipients with recurrent HCV who achieved SVR but had residual fibrosis, overall stability in Ishak fibrosis stage was similar between emricasan and placebo groups at 24 months (p=NS). However, there was improvement and/or stability in fibrosis stage in the pre-specified F3-F5 subgroup with emricasan vs. placebo (p=0.01), suggesting that patients with moderate fibrosis may further benefit with emricasan. Over 24 months, in combination with immunosuppression, tolerability and safety profiles were similar in both groups.