International Liver Congress
International Liver Congress
April 13, 2019
2 min read

Emricasan reduces portal pressure in cirrhosis despite missing endpoint

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VIENNA — Emricasan missed its primary endpoint of hepatic venous pressure gradient reduction in all patients with nonalcoholic steatohepatitis-related compensated cirrhosis and severe portal hypertension but showed meaningful reductions in portal pressure among patients with high-risk disease, according to a presentation at the International Liver Congress 2019.

“Severe portal hypertension in cirrhosis is a key driver of decompensation and decompensation, in turn, is a key driver of death,” Guadalupe Garcia-Tsao, MD, from Yale University in Connecticut, said during her presentation. “We have recently shown that decreases in [hepatic venous pressure gradient (HVPG)] as small as 1 mmHg have been associated with a reduction in risk for decompensation or death.”

Previously, the oral pan-caspase inhibitor emricasan showed decreases in portal pressure and improved survival in cirrhosis models along with reductions in HVPG in patients with cirrhosis who had HVPG of 12 mmHg or higher.

In this phase 2b study designed to confirm these effects, Garcia-Tsao and colleagues randomly assigned 263 patients to receive 5 mg (n = 65), 25 mg (n = 65) or 50 mg (n = 66) of emricasan or placebo (n = 67) twice daily for 48 weeks. The primary endpoint of HVPG reduction was measured at 24 weeks.

While the endpoint was not met in all patients, a post-hoc analysis showed that HVPG decreased in treated participants with compensated cirrhosis who had HVPG of 16 mmHg or higher compared with placebo.

The mean changes from baseline in the patients with high-risk disease were –1.6 mmHg (5 mg group), –1.7 mmHg (25 mg group), –1.5 mmHg (50 mg group) compared with an increase of 0.5 mmHg in the placebo group (P < .05 for each treatment group vs. placebo).

Additionally, alanine aminotransferase decreased by 3 U/L to 5 U/L and aspartate aminotransferase decreased by 2 U/L to 6 U/L in most treated patients compared with placebo (P < .05).

Treatment-related adverse events were similar between treated groups and placebo. Severe adverse events occurred in 17.9% of treated patients and 11.9% of the placebo group.

“We await completion of the 48-week study for full safety data and clinical outcome events,” Garcia-Tsao said. “These results support additional exploration of emricasan in patients with severe portal hypertension.” – by Talitha Bennett



Garcia-Tsao G. Abstract LB-01. Presented at: International Liver Congress; April 10-14, 2019; Vienna, Austria.


Disclosures: Garcia-Tsao reports being a consultant for Biovie, Conatus, Enterome, Galectin, Genfit, Intercept and has received research grant funding from Intercept. Conatus funded the present study.