Emricasan safely reduces MELD score, other biomarkers in cirrhosis

Conatus Pharmaceuticals Inc. announced results from its phase 2 clinical trial of emricasan, which showed reduced MELD score, caspase-cleaved cytokeratin 18 serum and other biomarkers in patients with liver cirrhosis treated with emricasan vs. placebo.

The trial was conducted across 26 U.S. clinical sites and enrolled 86 patients with compensated liver cirrhosis, according to a press release. The patients underwent treatment with 25 mg of emricasan (Conatus, n = 44), an active caspase protease inhibitor, twice a day for 3 months or placebo (n = 42).

Among patients who received emricasan, reduced levels of caspase-cleaved cytokeratin 18 (cCK18, – 4.6%), caspase 3/7 (– 45.5%), full-length CK18 (flCK18, – 18%), alanine aminotransferase (– 3) and aspartate aminotransferase (– 5) were observed after 3 months of treatment compared with baseline. In patients who received placebo, cCK18 and caspase 3/7 levels increased by 9.3% and 8.8% from baseline, whereas flCK18, ALT and AST levels decreased compared to baseline, but at a lesser rate than patients who received emricasan.

In addition, all patients who received emricasan experienced reduced MELD score (– 0.1), Child-Pugh score (– 0.2), total bilirubin (– 0.05) and international normalized ratio (– 0.02) compared with patients who received placebo who experienced increases in all categories.

“The improvement after only 3 months of treatment in patients with cirrhosis and impaired hepatic function in nearly all of the mechanism-specific and mechanism-independent biomarkers, as well as favorable overall trends driven by statistically significant subgroup improvements in clinically relevant markers of liver function — MELD and Child Pugh scores — is highly encouraging,” David T. Hagerty, MD, executive vice president of clinical development at Conatus, said in the release. “The magnitude of the treatment effect was much more meaningful in patients with high baseline MELD scores.”

Researchers also observed improvements in these biomarkers among a subgroup of patients with MELD scores of 15 or more at baseline. These improvements included a 1.6 reduction in mean MELD score in patients treated with emricasan vs. 0.6 increase with placebo (P = .003), and 0.6 reduction in mean Child-Pugh score with emricasan vs. 0.6 increase in patients treated with placebo (P = .003), according to the release.

“The two latest clinical trials demonstrate emricasan's ability to provide statistically significant improvements rapidly in clinically important validated surrogate endpoints of portal hypertension and liver function in the subgroups of patients with highest medical need,” Steven J. Mento, PhD, president and CEO of Conatus, said in the release.

Disclosure: Hagerty and Mento are employed by Conatus.