Gilead to take selonsertib into phase 3 in NASH

Gilead is to take its selonsertib into late stage trials in the hotly-contested fatty liver disease, non-alcoholic steatohepatitis (NASH) market, but abandoned further development in two other indications.

California-based Gilead announced top-line data from three phase 2 studies of selonsertib, also known as GS-4997, an investigational inhibitor of apoptosis signal-regulating kinase in NASH, pulmonary arterial hypertension (PAH), and diabetic kidney disease (DKD).

The anti-fibrotic activity demonstrated in the phase 2 NASH trial, which met its primary endpoint, was enough to convince Gilead to take a chance on late-stage development.

Not so in PAH and DKD, where there was insufficient evidence of efficacy, and Gilead has decided against further development in these indications.

Norbert Bischofberger, executive vice president, research and development and chief scientific officer, Gilead Sciences, said: “We are committed to advancing our pipeline of investigational molecules that separately target metabolic dysfunction, inflammation and/or fibrosis associated with NASH.”

“We are encouraged by these data demonstrating the anti-fibrotic effect of GS-4997 in patients with NASH after only 24 weeks of treatment, and look forward to sharing the complete results with the hepatology community.

"Additionally, pending discussions with regulatory agencies, we plan to initiate a phase 3 clinical trial programme of GS-4997 in patients with NASH.”

The GS-US-384-1497 trial combined GS-4997 alone or in combination with simtuzumab in 72 patients with NASH and fibrosis stages F2-F3.

Patients were randomised to receive GS-4997 6mg, GS-4997 6mg and simtuzumab 125mg, GS-4997 18mg plus simtuzumab 125mg, or simtuzumab alone for 24 weeks.

No differences were observed between the combination and monotherapy, and Gilead did not disclose its future plans for simtuzumab.

Data from the the GS-US-223-1015 phase 2 study in DKD showed GS-4997 was ineffective, and the drug also failed to meet endpoint in the ARROW phase 2 study in PAH.

Other pharma companies targeting NASH include Shire, Allergan and Intercept.