Pockros PJ et al. (2007) Oral IDN-6556, an antiapoptotic caspase inhibitor, may lower aminotransferase activity in patients with chronic hepatitis C. Hepatology 46: 324–329

Apoptosis is a feature of many human liver diseases. IDN-6556 is an inhibitor of caspases, enzymes that promote apoptosis. Pockros et al. investigated the safety and efficacy of oral IDN-6556 in 105 patients with hepatitis B, hepatitis C, primary biliary cirrhosis, nonalcoholic steatohepatitis or primary sclerosing cholangitis. Hepatitis C patients were given 5–200 mg doses 1–3 times/day (maximum dose 400 mg/day) for 2 weeks; patients with other diseases received 100 mg/day; 79 patients received active drug and 26 received placebo.

For patients with hepatitis C, all IDN-6556 doses >5 mg/day significantly lowered serum alanine aminotransferase and aspartate aminotransferase levels compared with placebo; enzyme levels were reduced by up to 56%. Split dosing seemed to be more effective than single doses; almost 50% of patients who received twice or three times daily doses normalized their aminotransferase levels, compared with 20% of those on once-daily dosing. No other dose–response relationship was noted. Although statistical analysis was not performed on data from the other disease groups, aminotransferase levels were also lowered in hepatitis B and steatohepatitis patients; results in patients with cholestatic disease, however, were unclear.

No increase in viral load was observed in patients with hepatitis B or C infection, and no treatment-related adverse effects were reported. The authors conclude that IDN-6556 significantly lowers serum aminotransferases in hepatitis C patients, and is well tolerated. Longer-term studies are needed to further evaluate efficacy and safety, in particular the possible cancer risk from this powerful antiapoptosis agent.