SAN DIEGO, Jan. 11, 2016 (GLOBE NEWSWIRE) -- Conatus Pharmaceuticals Inc. (NASDAQ:CNAT) today announced the initiation of active patient recruitment in ENCORE-NF, a randomized, double-blind, placebo-controlled, Phase 2b clinical trial evaluating emricasan, the company’s first-in-class, orally-active pan-caspase inhibitor, in approximately 330 patients with biopsy-confirmed nonalcoholic steatohepatitis (NASH) and stage 1 to 3 fibrosis using the NASH Clinical Research Network (CRN) Histologic Scoring System. This trial is designed to evaluate differentiated dosing and establish efficacy of emricasan in the large and growing NASH fibrosis market as well as add long-term safety data in support of the company’s initial registration focus in liver cirrhosis.
The ENCORE-NF clinical trial is expected to be conducted at approximately 90 U.S. and EU clinical sites. Patients will be randomized 1:1:1 to receive 5 mg of emricasan, 50 mg of emricasan, or placebo twice daily for 72 weeks. The 5 mg and 50 mg doses have previously been shown to be equally effective in reducing ALT, AST and mechanism-specific biomarkers in patients with liver fibrosis, while the 50 mg dose may provide additional benefit in patients with liver cirrhosis. The primary endpoint is a biopsy-based improvement in fibrosis by at least one stage vs. placebo using NASH CRN without worsening of steatohepatitis. Secondary endpoints include resolution of steatohepatitis without worsening of fibrosis, nonalcoholic fatty liver disease (NAFLD) activity score (NAS) and its components (steatosis, lobular inflammation, and ballooning), collagen and fat content by biopsy, key serum biomarkers, and health-related quality of life, as well as safety and tolerability of emricasan. Top-line results from the ENCORE-NF clinical trial are expected in 2018.
“With ENCORE-NF, we are evaluating emricasan’s potential to provide histological benefit and product differentiation in these patients to establish a development path forward in NASH fibrosis,” said Conatus co-founder, President and Chief Executive Officer Steven J. Mento, Ph.D. “Emricasan’s mechanism of action targets both apoptosis and inflammation, both of which are key drivers of liver fibrosis in NASH. In preclinical models of NASH and NAFLD, emricasan treatment improved liver histology, including reductions in both liver fibrosis and liver inflammation. Emricasan also reduced mechanism-specific biomarkers and serum levels of ALT and AST. In our NAFLD/NASH clinical trial reported in 2015, emricasan treatment afforded statistically significant reductions in ALT, AST and in mechanism-specific biomarkers. We believe these combined results provide a strong scientific rationale supporting the clinical development of emricasan in patients with NASH fibrosis.”
The ENCORE-NF clinical trial is the first of multiple parallel EmricasaN, a Caspase inhibitOR, for Evaluation (ENCORE) Phase 2b clinical trials designed to evaluate multiple doses of emricasan over various treatment durations in chronic liver disease of different etiologies and disease stages. The ENCORE trials are designed to provide clinically relevant efficacy, dosing, and safety data to support the initial registration of emricasan for chronic administration in patients with liver cirrhosis. Results from the combined ENCORE clinical trials are expected to support the design of Phase 3 efficacy and safety trials, but could warrant earlier discussions with regulatory agencies regarding potential accelerated approval. Conatus expects to initiate the remainder of these trials on a staggered basis through early 2017 and expects top-line results from the ENCORE clinical trials to be available periodically beginning in the first half of 2018.
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. Recent emricasan clinical trial results have demonstrated emricasan’s ability to provide statistically significant improvements in clinically important validated surrogate endpoints of portal hypertension and liver function across a variety of etiologies in the subgroups of liver cirrhosis patients with highest medical need. 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 hepatitis C virus (HCV) infection and who have successfully achieved a sustained viral response (SVR) following antiviral therapy (POLT-HCV-SVR).
About Conatus Pharmaceuticals
Conatus is a biotechnology company focused on the development and commercialization of novel medicines to treat liver disease. Conatus is developing its lead compound, emricasan, for the treatment of patients with chronic liver disease. 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, emricasan has the potential to interrupt the disease progression across the spectrum of liver disease. For additional information, please visit www.conatuspharma.com.
Forward-Looking Statements
This press release contains forward-looking statements within the meaning of Section 21E of the Securities Exchange Act of 1934, as amended. All statements other than statements of historical facts contained in this press release are forward looking statements, including statements regarding: enrollment in the ENCORE-NF trial; the use of the ENCORE-NF trial to evaluate differentiated dosing and establish efficacy of emricasan and add long-term safety data for the company’s initial registration in liver cirrhosis; emricasan’s potential benefit at the 50 mg dose in patients with liver cirrhosis; the expected availability of top-line results from the ENCORE-NF trial in 2018; the potential differentiation of emricasan dosing based on stage of liver disease to establish a development path forward in NASH fibrosis; the potential efficacy and safety of emricasan in various liver disease patient populations; the company’s initial registration focus in liver cirrhosis; the size and scope of the ENCORE-NF clinical trial; the predictive value of past preclinical results and clinical results in other patient populations on potential results in NASH fibrosis patients; the ability of the ENCORE trials to provide clinically relevant efficacy, dosing confirmation, and safety data to support the initial registration of emricasan for chronic administration in patients with liver cirrhosis and support the design of Phase 3 trials; the ability of the ENCORE trials to warrant discussions with regulatory agencies regarding potential accelerated approval; the planned initiation of the ENCORE trials through early 2017 and expected results beginning in the first half of 2018; and emricasan's potential to interrupt the disease progression across the spectrum of liver disease. In some cases, you can identify forward-looking statements by terms such as “may,” “will,” “should,” “expect,” “plan,” “anticipate,” “could,” “intend,” “target,” “project,” “contemplates,” “believes,” “estimates,” “predicts,” “potential” or “continue” or the negative of these terms or other similar expressions. These forward-looking statements speak only as of the date of this press release and are subject to a number of risks, uncertainties and assumptions, including: Conatus’ ability to initiate and successfully complete current and future clinical trials; and those risks described in Conatus’ prior press releases and in the periodic reports it files with the Securities and Exchange Commission. The events and circumstances reflected in Conatus’ forward-looking statements may not be achieved or occur and actual results could differ materially from those projected in the forward-looking statements. Except as required by applicable law, Conatus does not plan to publicly update or revise any forward-looking statements contained herein, whether as a result of any new information, future events, changed circumstances or otherwise.