SAN DIEGO, Sept. 2, 2014 (GLOBE NEWSWIRE) -- Conatus Pharmaceuticals Inc. (Nasdaq:CNAT), a biotechnology company focused on the development and commercialization of novel medicines to treat liver disease, today announced the initiation of a Phase 2 clinical trial of its lead drug candidate, emricasan, in patients with liver cirrhosis (LC), and the initiation of a separate exploratory Phase 2 trial in cirrhosis patients with portal hypertension (PH).
The Phase 2 LC clinical trial is designed to consist of two phases and enroll approximately 80 subjects at approximately 20 sites in the United States. In the first phase, which is double-blind and placebo-controlled, subjects will be randomized 1:1 to receive either 25 mg of emricasan or placebo orally twice daily for three months. In the second phase, which will be open label, subjects who complete the first phase of the trial, either on treatment or placebo, may receive emricasan for up to an additional three months. Top-line data from the first phase of this trial are expected to be available in the second half of 2015.
Inclusion criteria will include clinical, radiological, or biochemical evidence of liver cirrhosis and a Model for End-Stage Liver Disease (MELD) score of 11 to 18 during the screening period. The primary endpoint will be change from baseline in cleaved cytokeratin 18 (cCK18), a mechanism-specific biomarker of apoptosis associated with excessive cell death, which contributes to chronic inflammation. Secondary endpoints will include change from baseline in MELD score and change from baseline in Child-Pugh score, an assessment of the prognosis of chronic liver disease, primarily cirrhosis. The clinical trial will also evaluate other key serum biomarkers and the safety and tolerability of emricasan in the target patient population.
The exploratory, open label Phase 2 clinical trial in PH patients is designed to enroll approximately 20 subjects at approximately eight sites in the United States. Inclusion criteria will include clinical, radiological, or biochemical evidence of liver cirrhosis and portal hypertension confirmed by hepatic venous pressure gradient (HVPG) procedure prior to enrollment. Subjects will receive 25 mg of emricasan orally twice daily for 28 days. The primary endpoint will be change from baseline in cCK18 and HVPG. Secondary endpoints will include change from baseline in MELD score and change from baseline in Child-Pugh score. The clinical trial will also evaluate other key serum biomarkers and the safety and tolerability of emricasan in the target patient population. Top-line data from this trial are expected to be available in the third quarter of 2015 and this open label trial may allow for interim data evaluations.
"Liver cirrhosis represents a high medical need segment of the liver disease spectrum," said Conatus President and Chief Executive Officer, Steven J. Mento, Ph.D. "Current treatment options are limited and designed to control symptoms in an attempt to keep a patient healthy enough until a suitable organ becomes available and the patient undergoes a liver transplant. We believe our new trials will provide important information regarding emricasan's potential to benefit cirrhosis patients and help us prioritize opportunities for Phase 3 clinical development and ultimately the pathway for the initial commercialization of emricasan."
About Liver Cirrhosis
Liver cirrhosis is a complication of chronic liver disease characterized by replacement of healthy liver tissue with scar tissue resulting in abnormal structure and function of the liver. Common clinical signs of cirrhosis include jaundice (yellowing of the skin), weakness and fatigue, itching and susceptibility to bruising. Complications in cirrhosis patients may include fluid retention beneath the skin (edema) and in the abdomen (ascites), bacterial infection in the abdominal cavity, increased blood pressure in the portal vein (portal hypertension) resulting in bleeding from dilated and weakened blood vessels (varices) in the adjacent areas of the esophagus, accumulation of ammonia and other toxins in the blood leading to impaired brain function (hepatic encephalopathy), and cascading failure of other internal organs including kidney, spleen and lungs, as well as liver cancer (hepatocellular carcinoma).
About Emricasan Clinical Development
Conatus is developing emricasan for the treatment of patients with chronic liver disease and acute exacerbations of chronic liver disease, including acute-on-chronic liver failure (ACLF), LC, PH, post-orthotopic liver transplant (POLT) recipients with reestablished liver fibrosis post-transplant as a result of recurrent hepatitis C virus (HCV) infection who have successfully achieved a sustained viral response (SVR) following HCV antiviral therapy (POLT-HCV-SVR), and nonalcoholic fatty liver disease (NAFLD), including patients with inflammatory and/or fibrotic nonalcoholic steatohepatitis (NASH). To date, emricasan has been studied in over 550 subjects in twelve clinical trials. In a completed Phase 2 clinical trial, emricasan consistently demonstrated clinically meaningful, statistically significant, rapid and sustained reductions in elevated levels of two key biomarkers of inflammation and cell death 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. Conatus is also supporting a pilot clinical study funded by the National Institute on Alcohol Abuse and Alcoholism (NIAAA) in patients with severe alcoholic hepatitis.
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 and acute exacerbations of chronic liver disease. Emricasan is a first-in-class, orally active caspase protease inhibitor designed to reduce the activity of enzymes that mediate inflammation and cell death, or 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 the expected numbers of patients, trial sites and enrollment periods for the Phase 2 clinical trials, top-line and interim data from the trials, emricasan's potential to provide benefit to patients with cirrhosis or patients with cirrhosis and portal hypertension, the timeline and the company's ability to prioritize opportunities for Phase 3 clinical development, the potential use of emricasan in multiple liver disease indications, and emricasan's potential to interrupt the progression 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: the potential for competing products to limit the clinical trial enrollment in the Phase 2 clinical trials, the company's ability to successfully enroll patients in and complete the Phase 2 clinical trials; the company's reliance on third parties to conduct its clinical trials, including the enrollment of patients, and manufacture its clinical drug supplies of emricasan; potential adverse side effects or other safety risks associated with emricasan that could delay or preclude its approval; 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 the company's prior press releases and in the periodic reports it files with the Securities and Exchange Commission. The events and circumstances reflected in the company's 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, the company 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.