Emricasan improves liver function in second stage of clinical trial

Conatus Pharmaceuticals Inc. announced positive results of the second stage of its phase 2 liver cirrhosis clinical trial, indicating emricasan, a pan-caspase inhibitor, improved liver function in patients with various etiologies of cirrhosis.

In the first stage of the phase 2 clinical trial, 86 patients with cirrhosis and baseline MELD scores between 11 and 18 were randomly assigned to receive either 25 mg of emricasan (Conatus Pharmaceuticals) or placebo orally twice daily for 3 months. In the open-label second stage, all patients either on emricasan or placebo received emricasan for an additional 3 months, according to a press release.

Of the patients enrolled and dosed, liver cirrhosis etiologies included alcohol (38%), hepatitis C virus infection (29%), nonalcoholic steatohepatitis (23%) and other causes (9%). Baseline MELD scores were less than 14 in 78% of patients and greater than 15 in 22%. Forty-three percent of patients had baseline Child-Pugh A and 56% had Child-Pugh B cirrhosis.

Overall population results showed liver function continued to improve after the second 3 months of treatment on emricasan following previously reported favorable trends with emricasan vs. placebo after the first 3 months. In addition, liver function continued to improve after the second 3 months of treatment on emricasan in a subgroup of patients with baseline MELD scores greater than 15. Patients with NASH had significantly improved liver function after the first 3 months of treatment, regardless of baseline MELD score.

“The subgroup analysis of NASH patients in the liver cirrhosis trial provided the first ever demonstration in NASH cirrhosis of liver function benefit in response to drug treatment,” Steven J. Mento, PhD, president and CEO of Conatus, said in the release, adding that Conatus will soon discuss plans with the FDA for a clinical trial in patients with NASH cirrhosis, with a goal of initiation in early 2017.

“The continued directional improvements in these measures of liver function after 6 months of treatment confirm the sustained activity of emricasan and support continued development in patients with cirrhosis,” David T. Hagerty, MD, executive vice president of Clinical Development at Conatus Pharmaceuticals, said in the release.

At the International Liver Congress, HCV Next Editorial Board member Catherine T. Frenette, MD, from Scripps Clinic, San Diego, reported interim results from stage 1 of the trial during the Late Breakers session.

“We saw consistent improvement in caspase-related biomarkers in the overall emricasan group,” Frenette said during her presentation. “There were also consistent improvements in transaminase levels in the overall emricasan group.”

In the overall population, Frenette said the decreases in MELD and Child Pugh scores appeared nonsignificant until subgroup analysis was performed and it emerged that these scores were impacted most in patients with MELD of 15 or higher. In the high MELD group, improvement in the active group vs. the placebo group were seen in MELD score (–1.6 vs. 0.6, respectively; P = .003), Child Pugh score (–0.6 vs. +0.6, respectively; P = .003), total bilirubin (–0.55 mg/dL vs. –0.06 mg/dL, respectively; P = .03), and INR (–0.14 vs. 0.06, respectively; P = .0004).

Disclosure: Hagerty and Mento are employed by Conatus Pharmaceuticals. Frenette reports receiving a grant as an investigator for Conatus Pharmaceuticals.