Cilofexor misses primary NASH endpoint, improves liver function in combination therapy

Results from the phase 2 ATLAS study showed that neither monotherapy nor combined therapy with cilofexor reached the endpoint of significant improvement in fibrosis stage without worsening of nonalcoholic steatohepatitis, according to a press release from Gilead Sciences.

However, patients treated with a combination of the acetyl-CoA carboxylase inhibitor firsocostat and the farnesoid X receptor agonist cilofexor achieved improvements in multiple response measures of fibrosis and liver function compared with placebo.

“This trial provides novel data showing consistent improvements in liver histology and noninvasive tests, demonstrating the value of a combination approach to deliver meaningful changes in fibrosis, the key determinant of disease severity in NASH,” Rohit Loomba, MD, MHSc, from the University of California, San Diego, said in the release.

The randomized control study comprised 392 patients with NASH-related advanced fibrosis who received monotherapy with cilofexor or firsocostat; combined therapy of selonsertib and firsocostat, selonsertib and cilofexor, or firsocostat and cilofexor; or placebo.

At 48 weeks, the primary endpoint of fibrosis stage improvement without worsening of NASH did not occur at significant rates in any treatment group compared with placebo. Additionally, NASH resolution without worsening of fibrosis was uncommon among all treatment groups.

A significant number of patients treated with firsocostat and cilofexor achieved secondary endpoints including 2-point or more reduction in nonalcoholic fatty liver disease activity score and 1-point or more reductions in steatosis, hepatocellular ballooning, and lobular inflammation.

The same treatment group also showed improvements in alanine aminotransferase, aspartate aminotransferase, bilirubin, and the Elevated Liver Fibrosis score compared with placebo.

Treatments were well-tolerated with most adverse events including mild to moderate pruritus, headache, diarrhea, and nausea.

“NASH is a complex disease driven by multiple mechanisms,” Merdad Parsey, MD, PhD, chief medical officer of Gilead Sciences, said. “The results from the ATLAS study suggest the potential for a combination therapeutic approach for patients with advanced fibrosis by targeting different aspects of this disease. We continue to analyze the ATLAS data and will work with regulators to determine appropriate next steps for these therapies.”

Reference: www.gilead.com