In December 2016, Conatus announced an exclusive option, collaboration and license agreement with Novartis for the global development and commercialization of emricasan.
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. We believe that by reducing the activity of these enzymes, emricasan has the potential to interrupt the progression of liver disease. To date, emricasan has been administered to over 600 subjects in eight Phase 1 and seven Phase 2 clinical trials, and has been generally well-tolerated in both healthy volunteers and patients with liver disease. Emricasan has also been extensively profiled in in vitro tests and studied in many preclinical models of human disease.
We are conducting a comprehensive clinical program to demonstrate the therapeutic benefit of emricasan across the spectrum of liver disease. We recently announced top-line results from our Phase 2 Portal Hypertension trial and the first stage of our Phase 2 Liver Cirrhosis trial, and currently have two active Phase 2 clinical trials:
- POLT-HCV-SVR: in post-orthotopic liver transplant (POLT) recipients with liver fibrosis or cirrhosis 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; and
- ENCORE-NF: in patients with non-alcoholic steatohepatitis (NASH) and liver fibrosis.
We expect the next milestones from our clinical development programs to be as follows:
We met with the FDA in May 2015 to discuss potential registration pathways for emricasan, including pathways based on validated surrogate endpoints published by the FDA in conjunction with AASLD that may be suitable for approval in cirrhosis, and received feedback on the proposed patient populations and methods of measuring and analyzing these endpoints. Based on communications with the FDA recommending single-etiology clinical trials, we plan to focus on advancing toward initial registration of emricasan for patients with cirrhosis due to NASH, with parallel development toward registration of emricasan for patients with NASH fibrosis.
In February 2016, we announced that the FDA granted Fast Track designation to the emricasan development program for the treatment of liver cirrhosis caused by NASH. The Fast Track program provides greater access to the FDA in order to expedite review of drugs that have demonstrated the potential to treat serious or life-threatening conditions.
We are pursuing a registration strategy with an initial focus in cirrhosis, with additional supportive long term safety data in patients with NASH fibrosis. Multiple parallel clinical trials, the EmricasaN, a Caspase inhibitOR, for Evaluation, or ENCORE trials, will evaluate a range of emricasan doses over various treatment durations in patients of different etiologies. We expect to initiate these trials on a staggered basis through early 2017 and expect top-line results to be available periodically beginning in the first half of 2018:
- ENCORE-PH: Expected to initiate in 2H16, a randomized, double-blind, placebo-controlled clinical trial to evaluate the effect of emricasan in reducing HVPG in patients with NASH cirrhosis and severe Portal Hypertension.
- ENCORE-LF: Expected to initiate in 1H17, a randomized, double-blind, placebo-controlled clinical trial to assess long-term Liver Function endpoints of MELD and CPT, related serum biomarkers and laboratory parameters associated with liver function, and to collect chronic administration safety information in patients with NASH cirrhosis and clinically significant portal hypertension.
- ENCORE-XT: An eXTension clinical trial that will continue treatment for at least an additional 18 months, for a total of at least two years, in patients who complete either the ENCORE-PH trial or ENCORE-LF trial – with continued monitoring for efficacy, safety, clinical outcomes and health-related quality of life.
- ENCORE-NF: Initiated in January 2016, a randomized, double blind, placebo-controlled clinical trial will evaluate the effect of emricasan in reducing fibrosis and steatohepatitis in patients with NASH Fibrosis but not cirrhosis. Treatment will be for 18 months. The primary endpoint will be a biopsy-based change in fibrosis by at least one stage using the NASH Clinical Research Network Histologic Scoring System, without worsening of steatohepatitis.
These trials are designed to provide statistically significant and clinically relevant efficacy data, dosing confirmation, and safety data to support chronic administration. We believe the combined ENCORE trials will support the design of Phase 3 efficacy and safety trials. We also believe the ENCORE trials could warrant discussions with regulatory agencies regarding potential accelerated approval if the resulting efficacy and safety data are sufficiently robust. However, the decision to pursue such an accelerated approval will depend on multiple factors, including the size of the efficacy and safety database, the strength of the efficacy data, the adequacy of the dose ranging data, and the regulatory agencies’ acceptance of a surrogate endpoint for trials of emricasan in patients with liver cirrhosis.