NASH Scorecard So Far This Year: A Look At The Hits & Misses

The recent failure of Conatus Pharmaceuticals’ (NASDAQ:CNAT) phase IIb ENCORE-NF study in patients with biopsy-confirmed nonalcoholic steatohepatitis (NASH) and liver fibrosis once again puts the spotlight on this promising but challenging space.

Earlier, biotech bigwig Gilead Sciences, Inc. (NASDAQ:GILD) had suffered a setback with the failure of a late-stage study on pipeline candidate, selonsertib, in patients with compensated cirrhosis (F4) due to NASH. STELLAR-4, a phase III, randomized, double-blind, placebo-controlled study (n=877), evaluated the safety and efficacy of selonsertib, which is an investigational, once-daily, oral inhibitor of apoptosis signal-regulating kinase 1 (ASK1), in patients with compensated cirrhosis due to NASH. However, the study did not meet the pre-specified 48-week primary endpoint of a ≥ 1-stage histologic improvement in fibrosis without worsening of NASH. The failure of the STELLAR-4 study is disappointing, given the significant market potential of NASH and increasing competition.

Notwithstanding the failures, the market for NASH holds potential and is expected to be targeted by most large pharma/biotech companies in 2019. It is poised to witness rapid growth unlike other lucrative yet saturated markets like cancer.

More on NASH

A chronic liver disease, NASH is caused by excessive fat accumulation in the liver or steatosis. Per records, it has affected up to 15 million people in the United States and could cause inflammation, hepatocellular injury, progressive fibrosis and cirrhosis. The ailment is anticipated to be the leading reason behind liver transplantation by 2020. Currently, NASH is the primary reason for liver transplants in people under 50 in the United States. Such patients also suffer from obesity and type II diabetes. With no treatments currently approved to address this disease, the market opportunity is substantially huge and many companies are investing a major chunk of their R&D budget on the same.

Pharma Players That Have a Lead in NASH

The recent failures underscore the complexity of the treatments being developed. The winner so far in the NASH race seems to be Intercept Pharmaceuticals, Inc (NASDAQ:ICPT) . The company recently announced positive top-line results from its pivotal phase III REGENERATE study of obeticholic acid (OCA) on patients with liver fibrosis due to NASH. The company stated that the primary endpoint of the study — fibrosis improvement without worsening of NASH at 18 months — was achieved with the 25 mg daily dose of OCA.

Also, a numerically greater proportion of patients in both OCA treatment arms (taking doses of 10 mg and 25 mg) met the primary endpoint of NASH resolution with no deterioration of liver fibrosis compared to placebo. The study was required to attain one of the two primary goals, per FDA, which it did. Intercept plans to file for an approval for OCA as a NASH treatment both in the United States and in Europe during the second half of 2019.

France-based, Genfit’s lead candidate elafibranor, which is in late-stage studies, also holds promise. A phase III study, RESOLVE-IT is evaluating the efficacy and safety of elafibranor 120 mg versus placebo in patients with NASH and fibrosis. In December 2018, the Data Safety Monitoring Board (DSMB) recommended the continuation of RESOLVE-IT without any modifications, based on the pre-planned review of safety data, including adverse events and laboratory data. The company expects to report top-line data by the end of 2019. Earlier in the month, the company announced protocol clearance by the FDA for a phase II study evaluating elafibranor in children and adolescents with non-alcoholic steatohepatitis

Allergan plc (NYSE:AGN) too has an interesting candidate in its pipeline, cenicriviroc, for the treatment of NASH. The 2016 Tobira Acquisition added the candidate to its pipeline. The candidate is being evaluated in a phase III study, AURORA. Results from the study are not expected before 2020.

Viking Therapeutics (NASDAQ:VKTX) is another company, which has a promising NASH candidate, VK2809, in its pipeline.

Other Entrants

Given the fact that it is a lucrative market, quite a few companies have inked deals to enter this space. Novartis AG (NYSE:NVS) entered into a clinical development agreement with Pfizer (NYSE:PFE). The agreement includes a clinical trial to evaluate the combination of tropifexor (LJN452) and one or more Pfizer compounds for the treatment of NASH. Pharma giant Merck (NYSE:MRK) exercised its option to license NGM313, an investigational monoclonal antibody agonist of the β-Klotho/FGFR1c receptor complex that is currently being evaluated for the treatment of NASH and type 2 diabetes.

Bottom Line

Given the huge market potential, we expect a lot of activity in this space going forward. Approval of any of the candidates will attract more players and investment to this corner of the healthcare space.

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