Conatus Pharmaceuticals Announces Top-line Results from Phase 2b POLT-HCV-SVR Clinical Trial
Biopsy-based Proof of Concept in Liver Fibrosis and Cirrhosis Supports Further Evaluation
Conference Call and Webcast Presentation at
Patients were stable transplant recipients who were an average of seven years post-transplant on chronic immunosuppression. Hepatitis C virus (HCV), the initial cause of the inflammatory insult to the transplanted liver, was eliminated by antiviral therapies prior to the study.
This is the first demonstration of the anti-fibrotic efficacy with emricasan using a histology endpoint in patients with fibrosis. Consistent with the previous 16 clinical trials, emricasan was generally well-tolerated in the POLT-HCV-SVR clinical trial, and the overall safety profile was similar in the emricasan and placebo groups.
A descriptive summary of the observed response rates (patients with both a baseline and two-year biopsy) after two years of dosing for different stages of fibrosis is provided below. All p values noted are ad hoc, as prospective statistical powering was not feasible in this previously unstudied patient population.
Analyses of Overall Population and Prespecified Subgroups
|Ishak Fibrosis Score at Baseline||Emricasan
|Overall Population||77.4 (24/31)||75.0 (15/20)||2.4||0.842|
|F2*||83.3 (5/6)||100 (5/5)||-16.7||1.000|
|F2, F3, F4||92.0 (23/25)||66.7 (10/15)||25.3||0.081|
|F3, F4||94.7 (18/19)||50.0 (5/10)||44.7||0.011|
|F3, F4, F5*||95.0 (19/20)||58.3 (7/12)||36.7||0.019|
|F2, F3, F4, F5||92.3 (24/26)||70.6 (12/17)||21.7||0.093|
|F6*||0 (0/5)||100 (3/3)||-100||0.018|
*Prespecified subgroup population
Emricasan provided evidence of an anti-fibrotic treatment effect in the prespecified subgroup of patients with advanced fibrosis or early cirrhosis (F3-F5 at baseline), with 95.0% of patients (19/20) in the emricasan arm achieving responses in Ishak Fibrosis Score after two years of treatment, compared with 58.3% (7/12) in the placebo arm, a 36.7 percentage point difference in response rate (p<0.02). Inflammatory activity markers (ALT, cCK18, flCK18, Knodell activity index components) were either normal or only slightly elevated at baseline in both the emricasan and placebo groups.
“We are most grateful to the patients who participated in the trial, which required three biopsy procedures over a two-year period,” said
The POLT-HCV-SVR trial, initiated in the second quarter of 2014, enrolled post-orthotopic liver transplant (POLT) recipients whose transplanted livers were damaged by recurrent HCV infection. They subsequently achieved a sustained viral response (SVR) following HCV antiviral therapy, but their transplanted livers had residual fibrosis or cirrhosis (baseline Ishak Fibrosis Score of F2 to F6). Patients were randomized 2:1 to receive 25 mg of emricasan, the company’s first-in-class, orally active pan-caspase inhibitor, or placebo, twice daily for two years. Biopsies were taken at baseline, after one year of treatment, and after two years of treatment.
The primary endpoint was defined as the difference in percentage of responders between the treatment and placebo arms at the two-year biopsy compared with the baseline biopsy. A response was defined as improvement or stability in Ishak Fibrosis Score for patients with baseline scores of F2 to F5 or improvement in Ishak Fibrosis Score for patients with baseline scores of F6. The prespecified goal was a difference of 15 percentage points or more in response rates between the treatment and placebo arms.
POLT-HCV-SVR studied a separate patient population versus the other three Phase 2b clinical trials in the company’s collaboration with
- ENCORE-PH (for Portal Hypertension), initiated in the fourth quarter of 2016, in approximately 240 patients with NASH cirrhosis and severe portal hypertension, with top-line results expected in the second half of 2018;
- ENCORE-NF (for NASH Fibrosis), initiated in the first quarter of 2016, in approximately 330 patients with NASH fibrosis, with top-line results expected in the first half of 2019; and
- ENCORE-LF (for Liver Function), initiated in the second quarter of 2017, in approximately 210 patients with decompensated NASH cirrhosis, with top-line results expected in the second half of 2019.
Conatus will host a conference call and webcast at
Conatus is a biotechnology company focused on the development and commercialization of novel medicines to treat liver disease. In collaboration with
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: further evaluation of emricasan based on the POLT-HCV-SVR trial results; emricasan’s potential treatment effect and anti-fibrotic efficacy; plans for evaluation of additional subgroups in a variety of secondary and exploratory endpoints; the timelines to announce results from the ENCORE clinical trials in 2018 and 2019; and caspase inhibitors' potential to interrupt the progression of a variety of diseases. 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: reported top-line results are based on preliminary analysis of key data and as a result, such top-line results may change following a more comprehensive review and may not accurately reflect the complete results of the clinical trial; Conatus’ ability to successfully enroll patients in and complete its ongoing clinical trials;
Source: Conatus Pharmaceuticals Inc.