The results featured in the Conatus late-breaker presentation were included among the notable developments in cirrhosis by Jaime Bosch, M.D., Ph.D., Professor of Medicine, Liver Unit, Hospital Clínic-IDIBAPS, University of Barcelona; and Guest Professor at Inselspital, Bern University, Switzerland, in his address at the closing general session of The International Liver Congress™ 2016 on Sunday.
“The results from the first stage of this trial in patients with cirrhosis and elevated MELD score showed that after only three months, emricasan treatment improved measures of liver function and prognosis [Model for End-stage Liver Disease (MELD) and Child Pugh scores] in patients with baseline MELD scores of 15 or higher,” said Dr. Frenette, “with a reassuring safety profile that was generally balanced compared to placebo. The importance of these results is reflected in their selection for a late breaker oral presentation at The International Liver Congress™ 2016, and in their recognition by Dr. Bosch. I am pleased to represent the investigators in presenting these data and am excited about the potential of this therapy to provide clinical benefit for patients with cirrhosis who have few options besides liver transplant, which is a major procedure with its own risks and challenges.”
Conatus co-founder, President and Chief Executive Officer Steven J. Mento, Ph.D., said, “We are encouraged by the results from the first stage of our Liver Cirrhosis clinical trial, as detailed in Dr. Frenette’s late breaker oral presentation, and eager to evaluate the results after an additional three months of treatment in the second stage of the trial. Our commitment to the continued development of emricasan, a potentially disease-modifying drug candidate, is driven by the high unmet medical need in liver cirrhosis, especially among patients who have reached the transplant eligibility threshold of 15 or greater in MELD score.”
Liver Cirrhosis Trial
The double-blind, placebo-controlled Phase 2 Liver Cirrhosis clinical trial was conducted at 26 U.S. sites and enrolled 86 patients with liver cirrhosis due to different etiologies, mild to moderate liver impairment and baseline MELD scores of 11 to 18. In the double-blind and placebo-controlled stage, patients were randomized 1:1 to receive either 25 mg of emricasan or placebo orally twice daily for three months. The primary endpoint was change from baseline in cleaved Cytokeratin 18 (cCK18). Secondary endpoints included changes from baseline in MELD and Child-Pugh scores, which include laboratory parameters associated with liver synthetic and excretory function, such as serum albumin levels, international normalized ratio (INR) and total bilirubin levels. In the open-label stage, all patients either on emricasan or placebo receive emricasan for an additional three months. Six-month data from patients who continued treatment and three-month data from placebo patients who crossed over to emricasan treatment are expected in the second quarter of 2016.
About Emricasan Clinical Development
To date, emricasan has been studied in over 650 subjects in sixteen clinical trials across a broad range of liver disease etiologies and stages of progression. In multiple clinical trials, emricasan has demonstrated statistically significant, rapid and sustained reductions in elevated levels of key biomarkers of inflammation and apoptosis that are implicated in the severity and progression of liver disease. Importantly, these key biomarkers are known to be elevated and to have prognostic value in multiple hepatic indications that Conatus is currently pursuing. The company also is evaluating emricasan’s potential longer-term effects on liver structure in its ongoing Phase 2b clinical trial in post-orthotopic liver transplant (POLT) recipients who have reestablished liver fibrosis or cirrhosis post-transplant as a result of recurrent HCV infection and have successfully achieved a sustained viral response following HCV antiviral therapy (POLT-HCV-SVR). In November 2015, the company announced plans to conduct multiple clinical trials covering various liver cirrhosis patient populations for different chronic dosing periods using different endpoints – the EmricasaN, a Caspase inhibitOR, forEvaluation, or ENCORE trials – as a strategy for initial registration of emricasan as a potential treatment for patients with liver cirrhosis. In January 2016, Conatus announced the initiation of ENCORE-NF, the first of the ENCORE trials, a randomized, double-blind, placebo-controlled, Phase 2b clinical trial in patients with biopsy-confirmed nonalcoholic steatohepatitis (NASH) and stage 1 to 3 fibrosis using the NASH Clinical Research Network (CRN) Histologic Scoring System.