Gilead Sciences has announced positive interim results from the ongoing phase 3 study of its newly-acquired investigational treatment for primary biliary cholangitis (PBC), seladelpar.
Key in Gilead’s $4.3 billion CymaBay Therapeutics acquisition a few months ago, seladelpar is a first-in-class oral PPAR-delta agonist that regulates metabolic and liver disease pathways, influencing genes involved in bile acid synthesis, inflammation, fibrosis and lipid metabolism.
The phase 3 ASSURE study is an open-label trial involving 174 adult patients with PBC who had an inadequate response or intolerance to ursodeoxycholic acid, a medication to treat certain liver diseases. Over 12 months, 70% of the patients met the composite response endpoint, and 37% achieved normalization of alkaline phosphatase (ALP), with an average ALP reduction of 44%. Improvements in liver injury biomarkers included reductions in total bilirubin by 9%, gamma-glutamyl transferase by 36%, and alanine aminotransferase by 25%. Seladelpar was generally well-tolerated, with no treatment-related serious adverse events reported.
PBC is a chronic inflammatory liver disease that predominantly affects women, characterized by cholestasis and the accumulation of toxic bile acids, leading to liver inflammation and destruction of bile ducts. PBC patients often suffer from debilitating symptoms such as pruritus and fatigue, with progression increasing the risk of liver-related mortality.
Seladelpar's NDA for treatment of PBC is currently under priority review by the FDA, with a decision expected in August 2024. Additionally, the drug is under review by the UK's MHRA and the EMA. If approved, seladelpar has the potential to generate sales of $1.9 billion by 2029, according to LSEG data.
