Key Biomarker Data From Phase 1 Trial of Emricasan in Patients With Hepatic Impairment
SAN DIEGO, Nov. 10, 2014 (GLOBE NEWSWIRE) -- Conatus Pharmaceuticals Inc. (Nasdaq:CNAT) today is presenting its late-breaking poster at The Liver Meeting®, the annual meeting of the American Association for the Study of Liver Diseases (AASLD) in Boston November 7-11, 2014. The poster (#LB16), entitled "Rapid and statistically significant reduction of markers of apoptosis and cell death in subjects with mild, moderate and severe hepatic impairment treated with a single dose of the pan-caspase inhibitor, emricasan," will be available for viewing in the Poster Hall on the second floor of the John B. Hynes Convention Center today, Monday, November 10, 2014, from 8:00 a.m. to 5:30 p.m. ET and authors will be available for discussion at the poster from 12:30 p.m. to 2:00 p.m. ET. The poster is available on the Events & Presentation page in the Investor Center of the Conatus website at www.conatuspharma.com.
The poster highlights key secondary endpoint pharmacodynamic (PD) biomarker results from the company's recently completed Phase 1 hepatic impairment clinical trial. The trial was conducted in 12 subjects with mild, 8 subjects with moderate, and 8 subjects with severe hepatic impairment, as defined using Child-Pugh Scores, and 8 healthy matched control subjects. All subjects received a single 50 mg oral dose of emricasan, and serial blood samples were collected over a 48-hour period. Levels of three key biomarkers of apoptosis, overall cell death, and caspase enzymatic activity – caspase-cleaved cytokeratin 18 (cCK18), full-length cytokeratin 18 (flCK18), and caspase 3/7, respectively – were elevated at study baseline and demonstrated rapid and statistically significant reductions after a single 50 mg oral dose of emricasan. Importantly, levels of these three key biomarkers demonstrated significant reductions from the elevated levels at baseline in 100% of the hepatic impaired subjects compared with 0% of the matched control subjects, whose baseline levels were not elevated. In all three impaired groups, peak reductions of caspase 3/7 occurred approximately 4 hours after dosing, and peak reductions in cCK18 and flCK18 levels occurred 8 to 12 hours after dosing. All three biomarkers trended toward pre-dose levels within 24 to 48 hours after dosing. Noteworthy conclusions from the study included:
- Mechanism-specific biomarkers of apoptosis and caspase enzymatic activity, together with a biomarker of overall cell death, are elevated in subjects with advanced liver disease.
- Biomarker elevations were rapidly reduced after a single dose of emricasan in all hepatic impaired patients.
- Since elevation of these biomarkers is related to disease pathology and progression, emricasan may provide clinical benefit to patients with advanced stages of liver disease.
"We had previously demonstrated emricasan's ability to rapidly reduce disease-elevated biomarkers of caspase activity, apoptosis and overall cell death in patients with earlier-stage liver disease," said Conatus co-founder, Senior Vice President of Research and Chief Scientific Officer, Alfred P. Spada, Ph.D., "and we are pleased that the current study showed significant and rapid reductions in these biomarkers after a single dose of emricasan in patients in more advanced stages of liver disease. We believe these biomarkers measure key drivers in the progression of liver disease, and we look forward to completing our ongoing trials to determine whether biomarker reductions correlate with clinical benefits for patients."
Conatus initiated three clinical trials of emricasan in patients with impaired organ function to support dose selection and prioritization for advancement in its overall clinical development program: a Phase 2b trial initiated in September 2013 in acute-on-chronic liver failure (ACLF) patients who may have simultaneous impairment of both liver and kidney function; a Phase 1 trial initiated in January 2014 in patients with severe renal impairment; and the previously described Phase 1 hepatic impairment trial initiated in April 2014. Preliminary pharmacokinetic (PK) results from the renal impairment and hepatic impairment trials were used to support the design of two recently initiated trials in patients with liver cirrhosis. Aggregate final data from these three trials are expected to be sufficient to inform on optimal dosing of emricasan, and future direction for the clinical development of emricasan, in potential future studies over a broad range of patient populations, including critically ill patients with varying degrees of liver and kidney function.
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 ACLF, liver cirrhosis (LC), portal hypertension (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). 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. To date, emricasan has been studied in over 550 subjects in twelve clinical trials.
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 pan-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.
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 elevation of biomarkers related to liver disease pathology and progression, emricasan's potential to impact on the biomarkers and the progression of liver disease, the potential for the PK data to inform on optimal dosing of emricasan in future studies in potential target patient populations, the role of caspase activity and apoptosis in disease pathology and progression, and emricasan's potential to provide clinical benefit to patients across a broad spectrum of liver disease, including patients with advanced stages 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: dosing of emricasan beyond a single dose, the applicability of the biomarkers as potential drivers of liver disease progression, the effect on liver disease of decreasing the biomarkers, the determination of the most appropriate patients for enrollment in the company's Phase 2 clinical trial in patients with cirrhosis, the potential for competing products to limit the clinical trial enrollment in the company's Phase 2 clinical trials, the company's ability to successfully enroll patients in and complete its 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.