Conatus Phamaceuticals reported the phase IIb trial ENCORE-NF evaluating emricasan for Nonalcoholic steatohepatitis (NASH) did not meet the primary endpoints.
The randomized, double-blind ENCORE-NF trial enrolled and treated 318 patients with biopsy-confirmed NASH CRN fibrosis stages F1-F3 at baseline. Patients were randomized 1:1:1 to receive 5 mg of emricasan, 50 mg of emricasan, or placebo twice daily for 72 weeks. The trial was conducted at 87 U.S. and EU sites. The primary endpoint of the trial was greater or equal to 1 CRN fibrosis stage improvement with no worsening of steatohepatitis compared with placebo at week 72. The trial failed to meet the endpoint. The response rates were 11.2% for the 5 mg dose, 12.3% for the 50 mg cohort and 19% for the placebo groups. Statistically significant decreases in ALT and Caspase 3/7 were observed in the emricasan cohorts.
Conatus Pharmaceuticals plans to review additional data readouts over the coming months with collaborators at Novartis to determine the most appropriate path forward.
Conatus previously reported the Phase IIb ENCORE-PH trial for NASH and the Phase IIb POLT-HCV-SVR trial in liver transplant patients with fibrosis or cirrhosis both failed to meet the primary endpoints.
About Nonalcoholic Steatohepatitis (NASH)
Non-Alcoholic Steatohepatitis is the most severe form of non-alcoholic fatty liver disease (NAFLD), and is characterized by the presence of an abnormal accumulation of fat in the liver which in some individuals can progress to liver cell injury (hepatocellular ballooning) and inflammation. Hepatocellular ballooning and inflammation – sometimes called necroinflammation – are commonly considered as the drivers of disease progression, or as the underlying causes of the disease. As NASH evolves, over time it can result in excessive scarring in the liver (fibrosis), a natural response to injury which can lead to liver cirrhosis or liver cancer.
Emricasan is a first-in-class, orally active pan-caspase inhibitor designed to reduce the activity of enzymes that mediate inflammation and apoptosis. Conatus believes that by reducing the activity of these enzymes, caspase inhibitors have the potential to interrupt the progression of a variety of diseases.