Our strategy is to develop and commercialize medicines to treat liver disease and associated fibrotic and cirrhotic indications in areas of high unmet medical need. The key elements of our strategy are to:
Focus initial development of emricasan on the treatment of liver diseases with high unmet medical need and in small, identifiable and manageable patient populations.
We believe that by inhibiting the caspases responsible for inflammation and apoptosis in the liver, emricasan has the potential to stabilize and improve liver function and to slow liver disease progression in patients with liver cirrhosis. We are focusing our initial development of emricasan in high medical need patients with cirrhosis with varying degrees of liver function impairment. We expect the size and cost of the required clinical trials in these patients to be manageable for our company.
Pursue accelerated pathways for regulatory approval in the United States and the European Union.
Based on our initial development focus of emricasan on liver diseases with high unmet medical need in small, identifiable and manageable patient populations, we believe accelerated pathways for regulatory approval may be applicable in the United States and the EU. We plan to discuss our clinical development and regulatory strategy for emricasan with the U.S. Food and Drug Administration (FDA) and regulatory authorities in the EU.
Build our own sales and marketing capabilities to commercialize emricasan for indications that target small, identifiable and manageable patient populations in North America and Western Europe.
If emricasan is approved for one or more small, identifiable and manageable patient populations in North America and the EU, we intend to build our own commercial organization to market the product for these indications. Specifically, we plan to build a focused, specialized sales force to target the key physicians who treat these indications in these geographic locations, including hepatologists and other liver specialists in tertiary care and transplant centers.
Evaluate strategic partnerships to maximize the commercial potential of emricasan.
We plan to evaluate opportunities to partner emricasan with pharmaceutical companies that have established sales and marketing capabilities in regions outside of North America. We may also partner with a pharmaceutical company that has global capabilities to evaluate emricasan in larger patient populations with earlier stages of liver disease for which we believe it may also be effective, such as liver fibrosis from viral hepatitis, alcoholic hepatitis and NASH.
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.