With 29 Candidates Advancing, NASH Race May Hinge On Long-Duration Data

Even with market estimates that NASH drugs eventually could command sales of $35 billion a year, some of the candidates and companies now competing in the space will have to be weeded out.

With the first firm moving into a Phase III trial in non-alcoholic steatohepatitis, others will be quick to follow. During a May 21 call reviewing the NASH field, Deutsche Bank Markets Research discussed how data showing treatment results over a year or longer will help discern the candidates with the most promise.

According to BioMedTracker, there are 14 candidates for NASH in Phase II or III development and another 15 earlier in the pipeline.

As Intercept Pharmaceuticals Inc. gets ready to initiate a 2,500-patient Phase III trial of farnesoid X receptor agonist obeticholic acid (OCA) with a 72-week interim analysis, Deutsche Bank analyst Alethia Young told the call that the key inflection points will come when the various competitors “show their data in 1) NASH patients and 2) for treatment durations longer than a year.”

Only Intercept and Genfit SA, expected to be the next company to start pivotal trials, for its PPAR alpha/delta agonist GFT-505, have shown such data so far, Young added (Also see "With Phase III NASH Endpoints In Place, Intercept May Reach Market By 2018" - Pink Sheet, 19 May, 2015.). But over the next 12 months, she anticipates that Raptor Pharmaceutical Corp., Galmed Pharmaceuticals Ltd., Gilead Sciences Inc. and Tobira Therapeutics Inc. will have data readouts that could establish significant value for their NASH programs (see related story, (Also see "Intercept’s Phase III Endpoints May Not Apply To Other Firms’ NASH Programs" - Pink Sheet, 25 May, 2015.)).

Tobira says its Phase II dual CCR2/CCR5 antagonist cenicriviroc is the only NASH candidate that addresses both fibrosis and inflammation, an underlying cause of NASH and fatty liver disease. Raptor’s lysosomal cysteine transporter cysteamine bitartrate is in Phase IIb with a focus on pediatric NASH. The most advanced of Gilead’s several “shots on goal” in NASH is the LOXL2 antagonist antibody simtuzumab, while Galmed has Aramchol, which targets ATP-binding cassette transporter 1 and stearoyl-CoA desalurase 1, in Phase IIb (Also see "NASH Drugs Soon May Have A Registrational Pathway, Finally" - Pink Sheet, 30 Mar, 2015.).

A steady stream of deal-making has indicated that big pharma is monitoring the NASH competition and is interested in stepping in as well, Young noted. Novartis AG is working in the space with Phase II DGAT1 inhibitor pradigastat, while Merck & Co. Inc. has entered the competition by partnering with NGM Biopharmaceuticals Inc. on NGM282, which targets FGF19. In January, Gilead added to its NASH pipeline by partnering with Phenex Pharmaceuticals AG on a Phase II FXR agonist, the same mechanism as Intercept’s OCA (Also see "Deal Watch: Gilead’s Move Into NASH Highlights Post-Holiday Deal-Making" - Pink Sheet, 12 Jan, 2015.).

And the competition has not let up. On May 18, Boehringer Ingelheim GMBH exercised an option it took only two months before for Pharmaxis Ltd.’s Phase I PXS4728A, following Tobira’s lead by placing a bet on an anti-inflammatory approach to NASH [See Deal]. Enanta Pharmaceuticals Inc. recently announced its intent to bring a proprietary FXR agonist into clinical development by year’s end, as well.

Meanwhile, given the similar causality between metabolic syndrome and fatty liver disease, several companies have begun looking at approved drugs or candidates for diabetes as NASH therapies. As one example, Novo Nordisk AS presented Phase II data last month at the European Association for the Study of Liver Disease meeting on the potential of its GLP-1 receptor agonist Victoza (liraglutide) in NASH.

Young projects that the market for therapies to treat NASH with fibrosis ultimately could be larger than the opportunity in hepatitis C, to which NASH often is compared and contrasted (Also see "Intercept Thinks Fibrosis Effect Could Carry Its NASH Candidate" - Pink Sheet, 17 Nov, 2014.).

The domestic NASH population is estimated at between 18 million and 30 million people – it is currently poorly diagnosed because of a lack of biomarkers or other non-invasive ways of determining who has it. Young noted there are at least six NASH biomarkers in clinical development to provide an eventual diagnostic alternative to liver biopsy.

Similarly broad is the projection of how many Americans might have NASH complicated by advanced-stage fibrosis (F2 or F3). Current estimates peg this at between 2% and 15% of the U.S. population, Young noted.

“This may correspond to 5 million to 9 million people in the U.S. alone,” the analyst told the call. “This equals a major global problem driven by increasing diabetes and obesity. NASH happens more with these risk factors.” She projects the eventual NASH market ranging between $10 billion and $35 billion annually.