19 March 2021 - - US-based biopharmaceutical company Gilead Sciences, Inc. (NASDAQ: GILD) and Denmark-based healthcare company Novo Nordisk A/S (NASDAQ Copenhagen: NOVO B) have expanded their clinical collaboration in non-alcoholic steatohepatitis, the companies said.

The companies will conduct a Phase 2b double-blind, placebo-controlled study to investigate the safety and efficacy of Novo Nordisk's semaglutide, a GLP-1 receptor agonist, and a fixed-dose combination of Gilead's investigational FXR agonist cilofexor and investigational ACC inhibitor firsocostat, alone and in combination in people with compensated cirrhosis due to NASH.

The four-arm study in approximately 440 patients will evaluate the treatments' impact on liver fibrosis improvement and NASH resolution and will begin recruitment in the second half of 2021.

This new Phase 2b study builds on positive results from a Phase 2a proof-of-concept study presented at the Liver Meeting Digital Experience in November 2020 investigating semaglutide, alone and in combination with cilofexor and/or firsocostat, in 108 people with NASH and mild to moderate fibrosis.

The study met its primary endpoint, demonstrating that all regimens were well tolerated over 24 weeks.

The most common adverse events were gastrointestinal.

Across all groups, 5–14% of people discontinued any trial treatment due to adverse events.

In addition, post-hoc analyses of exploratory efficacy endpoints assessing biomarkers of liver health at 24 weeks showed statistically significant improvements in hepatic steatosis (measured by magnetic resonance imaging proton density fat fraction; MRI-PDFF) and liver injury (measured by serum alanine aminotransferase; ALT) in the combination treatment arms versus semaglutide alone.

Liver stiffness and the Enhanced Liver Fibrosis score declined in all groups; however, statistically significant differences between groups were not observed.

Cilofexor and firsocostat are investigational compounds and are not approved by the US Food and Drug Administration or any other regulatory authority.

Their safety and efficacy have not been established.

Semaglutide has not been approved by the FDA or any other regulatory authority for the treatment of patients living with NASH but has been approved for the treatment of type 2 diabetes.

NASH is a chronic and progressive liver disease characterised by fat accumulation and inflammation in the liver, which can lead to scarring or fibrosis, that impairs liver function.

The risk of progression to advanced liver disease, including liver decompensation (loss of liver function) and liver cancer, is higher in people with NASH than in the general population and NASH could become the leading reason for liver transplants in most countries.

Currently, no pharmacotherapy is globally approved for the treatment of NASH, and people with NASH are left with very few management options.