Oral IDN 6556, an Anti-Apoptotic Caspase Inhibitor, Lowers Aminotransferases in HCV Patients

Increased rates of apoptosis (programmed cell death) have been implicated in hepatic disease including HCV, NASH, HBV and PBC. IDN-6556 is a potent inhibitor of caspases, the proteases that execute apoptosis.

This multicenter, double-blind, placebo-controlled, dose-ranging study included 48 patients with chronic hepatitis C and 1 with NASH (ALT or AST: 1.5-10 x ULN).

Dosing: active drug N=37, placebo N=12, 6 dosing groups N=6 or 7. Dosing period: 14 days. Follow up: 21 days.

Results

All doses of drug significantly lowered ALT and AST (2-way ANOVA % change from baseline vs. Placebo: p<0.0001 at Day 14).

The decrease of ALT from baseline at day 14 for each dose was: -40% (25 mg QD), -33% (100mg QD), -35% (200mg QD), -49% (5 mg BID), -42% (50 mg BID) and -56% (100 mg BID).

The 100mg BID dose normalized ALT or AST in all 6 patients. Placebo patients did not change significantly (+2%). AST changes were similar.

Adverse experiences were generally mild and brief. 47/48 HCV patients had no changes in HCV RNA titers >1 log unit; one patient (IDN-6556, 100mg BID) showed complete viral clearance at the end of follow up. There were no other clinically meaningful changes in laboratory parameters.

Conclusions

Oral IDN-6556, given once or twice daily for 14 days, significantly lowered aminotransferases and appeared well tolerated. The trial is still ongoing. Further groups will include additional dose levels in HCV patients and 100mg BID doses in HBV, PBC and NASH patients.

05/24/04

Reference
E R Schiff and others.  Oral IDN-6556, an Anti-Apoptotic Caspase Inhibitor, Lowers Aminotransferases in HCV Patients. Abstract 126 (oral). Digestive Disease Week. May 15-20, 2004. New Orleans, LA.