Drug names: Selonsertib, firsocostat and cilofexor (in combination)
Mechanisms: ASK1 inhibitor, ACC inhibitor, FXR agonist
Stage: Phase 2
Next readout: ATLAS data expected by the end of 2019
Gilead’s ASK1 inhibitor, selonsertib, was among the front-runners of the NASH race—that is, until it failed to beat placebo in a pair of phase 3 studies that enrolled more than 1,600 patients with severe disease. One study looked at NASH patients with stage 3 fibrosis, while the other tested selonsertib in patients with cirrhosis, or stage 4 fibrosis. Though it stopped both trials early, the company is putting the data it collected to work in the development of noninvasive diagnostic tests for NASH, as well as improving the interpretation of liver biopsy.
In the meantime, it is testing selonsertib in combination with firsocostat and cilofexor in a phase 2 study. Gilead picked up the drugs from Nimbus Therapeutics and Phenex Pharmaceuticals, respectively. Firsocostat inhibits acetyl-CoA carboxylase (ACC) to prevent the production of key lipids in the liver, while cilofexor targets FXR, a nuclear receptor that regulates bile acid levels in the liver.
The company reported in April that the firsocostat-cilofexor combo led to improvements in liver stiffness, liver biochemistry, serum fibrosis markers and fat buildup in the liver in a small, 20-patient study. Gilead expects to report data from patients with stage 3 and 4 fibrosis in the phase 2 ATLAS study by the end of the year. It is also teaming up with Novo Nordisk to test the firsocostat-cilofexor combo with the latter’s GLP-1 drug semaglutide in a proof-of-concept study.
And that's not all: The Big Pharma is working to discover and develop up to five drug targets for NASH under a three-year partnership with Insitro. The goal is to better understand how NASH unfolds and come up with drugs that can affect the course of the disease. The duo is using Insitro’s technology, dubbed the Insitro Human platform, to create disease models of NASH and discover targets that affect the progression or regression of the disease.