Conatus Initiates Phase 2b ENCORE-PH Clinical Trial of Emricasan in Patients with NASH Cirrhosis
SAN DIEGO, Nov. 03, 2016 (GLOBE NEWSWIRE) -- Conatus Pharmaceuticals Inc. (NASDAQ:CNAT) today announced the initiation of ENCORE-PH (PH for Portal Hypertension), 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 240 patients with compensated or early decompensated liver cirrhosis caused by nonalcoholic steatohepatitis (NASH), and severe portal hypertension confirmed by hepatic venous pressure gradient (HVPG) of ≥12 mmHg at baseline. This trial is designed to evaluate dosing, efficacy and safety of emricasan in NASH cirrhosis as an integral part of the company's initial registration strategy. Top-line results from the ENCORE-PH clinical trial are expected in 2018.
The ENCORE-PH clinical trial is expected to be conducted at approximately 90 U.S. and EU clinical sites. Patients will be randomized 1:1:1:1 to receive 5 mg of emricasan, 25 mg of emricasan, 50 mg of emricasan, or placebo twice daily for 24 weeks. The primary endpoint is the mean change from baseline in HVPG at 24 weeks for each dosing group compared with the placebo group. Key secondary endpoints include safety and tolerability, dose response, and percentage of patients achieving at least a 20% reduction in HVPG. Additional key endpoints include initial or subsequent decompensation events, changes from baseline in Model for End-stage Liver Disease (MELD) and Child-Pugh scores, and health-related quality of life. Select sites will also investigate whether emricasan improves liver stiffness as measured by Fibroscan® transient elastography and liver metabolic function using the BreathID® Methacetin Breath Test at screening and at Week 24.
"ENCORE-PH is a key component of our clinical strategy designed to support an initial registration of emricasan in NASH cirrhosis," said Conatus co-founder, President and Chief Executive Officer Steven J. Mento, Ph.D. "Portal hypertension, a major consequence of advancing liver cirrhosis, is a driving factor in clinical outcomes such as ascites and variceal hemorrhage, as well as liver failure and death. The primary endpoint, HVPG, has been identified as a validated surrogate endpoint potentially suitable for registration. Results released last year from our open label pilot Portal Hypertension clinical trial and results from preclinical studies have demonstrated emricasan's ability to reduce HVPG rapidly and significantly through both intrahepatic and extrahepatic mechanisms. We believe that chronic administration of emricasan, which would be supported by the longer treatment duration being evaluated in ENCORE-PH, will lead to additional benefits for cirrhosis patients."
ENCORE-PH is one of the parallel EmricasaN, a Caspase inhibitOR, for Evaluation (ENCORE) clinical trials designed to evaluate emricasan treatment in chronic liver disease of different etiologies and disease stages. The ENCORE clinical 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 NASH cirrhosis and potentially support future label expansion. Results from the combined ENCORE clinical trials are expected to support the design of Phase 3 efficacy and safety trials and, depending on the strength of the efficacy and safety data, may warrant earlier discussions with regulatory agencies regarding potential accelerated approval. The ENCORE-NF clinical trial, in patients with NASH fibrosis, was initiated in January 2016. Conatus expects to initiate the remainder of the ENCORE clinical trials on a staggered basis through the first half of 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 ENCORE-NF clinical trial and its ongoing Phase 2b POLT-HCV-SVR 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.
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.
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: anticipated enrollment and number of sites in the ENCORE-PH clinical trial; the use of the ENCORE-PH clinical trial as part of the company's initial registration strategy; the availability of top-line results from the ENCORE-PH trial in 2018; the potential use of HVPG as a validated surrogate endpoint for registration; the potential benefit in cirrhosis patients from chronic administration of emricasan; the ability of the ENCORE trials to provide data to support the initial registration of emricasan, to support future label expansion, and to 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 the first half of 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; the predictive value of past preclinical and clinical results; results of future clinical trials of emricasan; the company's ability to obtain additional financing in order to complete the development and commercialization of emricasan; 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.
Source: Conatus Pharmaceuticals Inc.
Posted: November 2016