Emricasan reduces portal pressure in patients with cirrhosis

SAN FRANCISCO — A 28-day oral course of therapy with emricasan, a pan-caspase inhibitor, reduced portal pressure in patients with compensated cirrhosis and portal hypertension, according to Late Breaker data presented at The Liver Meeting 2015.

Guadalupe Garcia-Tsao, MD, of the VA-CT Healthcare System and Yale University in New Haven, Conn., conducted a proof-of-concept study in which 23 patients received 25 mg of oral emricasan (Conatus Pharmaceuticals) twice daily for 28 days. Patients were accrued at nine sites in the U.S., with nonalcoholic steatohepatitis and HCV being the majority cause of cirrhosis.

“The hypothesis was that emricasan would lower portal pressure and be safe in these patients,” Garcia-Tsao said during her presentation.

The change in hepatic venous pressure gradient (HPVG) served as the primary outcome. Overall, 22 patients completed the study.

The median HPVG was 13.5 mm Hg at baseline and 13 mm Hg after treatment. However, the researchers stratified patients by the HPVG treatment threshold of 12 mm Hg. In this analysis, patients with HPVG greater than 12 mm Hg showed a decrease of 17.2% in HPVG (P < .003).

Four of 12 patients experienced a 20% decrease or greater compared with eight of 12 experiencing a decrease of at least 10%. In two of these patients, HPVG decreased below 12 mm Hg.

Among the 10 patients with baseline HVPG less than 12 mm Hg, a 1.9 mm Hg increase occurred (P = .12). Similar findings played out with a cutoff of 10 mm Hg in a post-hoc analysis.

Blood pressure and heart rate remained unchanged for the whole cohort. All patients, particularly those with a baseline HVPG greater than 12 mm Hg, experienced significant reductions in alanine aminotransferase and aspartate aminotransferase levels. Other significant decreases were reported for serum levels of cCK18 and caspase 3/7.

One patient discontinued emricasan due to a nonserious adverse event. One patient experienced three serious adverse events 10 days after the dose of the study drug that were deemed “unrelated to treatment.”

“Emricasan administered orally for 28 days was associated with a significant decrease in portal pressure in patients with compensated cirrhosis and severe portal hypertension,” Garcia-Tsao concluded. “Although a hemodynamic mechanism cannot be ruled out, concomitant decreases in AST/ ALT suggest an intrahepatic anti-inflammatory effect.”

This data was previously reported in a manufacturer’s press release. – by Rob Volansky

Reference:

Garcia-Tsao G, et al. Abstract LB-6. Presented at: The Liver Meeting; Nov. 13-17, 2015; San Francisco.Disclosures: Garcia-Tsao reports being on the advisory committee or review panel of AbbVie and Fibrogen.