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New partners for NASH

New NASH targets and combinations will be in the spotlight at this year’s AASLD

Pharmas are loading up their NASH portfolios expecting that addressing the full disease spectrum will require combinations, though the field lacks the tools to sort the different mechanisms on offer strategically.

Meanwhile, at least three companies presenting at this year’s American Association for the Study of Liver Diseases (AASLD) meeting will have proof-of-concept data from new targets that could add to the clinical armamentarium and list of potential combination partners.

Combos have become a major component of pharmas’ strategies for non-alcoholic steatohepatitis (NASH), because the consensus view is that no single therapy can control the multifactorial processes driving most patients’ disease (see “Combo Deals”).

Dealmaking has become a core strategy, as pharmas build toolboxes that enable them to take a modular approach to tackling the disease.

The most recent example is the Oct. 29 deal in which Novartis AG will pair its farnesoid X receptor (FXR) agonist tropifexor with the three different mechanisms of action in Pfizer Inc.’s clinical NASH pipeline.

Zobair Younossi, chairman of the department of medicine at Inova Fairfax Hospital, compared NASH treatment to the diabetes landscape, where different therapies are added together to control individual patients’ disease processes.

“A regimen with a single drug is unlikely to be the answer for treating NASH in the long run. You probably have to target multiple different pathways at the same time,” he said.

However, finding the right combinations is challenging because many of the compounds’ mechanisms affect more than one of the metabolic, inflammatory or fibrotic aspects of NASH, and it’s not known which set of mechanisms will make the most difference for a given patient at a given time.

In addition, NASH lacks clear biomarkers, like HbA1c level in diabetes, to guide drug development and use, said

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