EFFICACY AND SAFETY OF SELADELPAR IN PATIENTS WITH PRIMARY BILIARY CHOLANGITIS AND COMPENSATED CIRRHOSIS IN THE PHASE 3 PLACEBO-CONTROLLED RESPONSE TRIAL

Introduction and Objectives

In the Phase 3 RESPONSE trial (NCT04620733), seladelpar, a first-in-class delpar (selective peroxisome proliferator–activated receptor delta agonist), significantly improved biomarkers of cholestasis in patients with primary biliary cholangitis (PBC) over 12 months vs placebo. More patients with cirrhosis met the primary endpoint in the seladelpar arm (39%) vs placebo (22%).

We now report data on additional biochemical results and safety in patients with or without cirrhosis in RESPONSE.

Patients and Methods

Eligible patients had an inadequate response or intolerance to ursodeoxycholic acid, alkaline phosphatase (ALP) ≥1.67 × ULN, and total bilirubin ≤2 × ULN; they received seladelpar 10 mg or placebo (2:1 randomisation) for 12 months. Cirrhosis was defined by medical history, liver biopsy, transient elastography, laboratory findings, and radiological features. Safety and changes in laboratory parameters were assessed.

Results

Of 193 patients, 27 (14%) had Child-Pugh A compensated cirrhosis at baseline (18 seladelpar, 9 placebo). Mean ALP change was −121.4 U/L for seladelpar vs 23.2 U/L for placebo patients with cirrhosis, and −134.8 U/L for seladelpar vs −18.0 U/L for placebo patients without cirrhosis. Greater decreases in other laboratory parameters were observed with seladelpar vs placebo regardless of cirrhosis status. Adverse events with seladelpar vs placebo were similar in patients with and without cirrhosis. No patients with cirrhosis discontinued seladelpar due to adverse events. Elevations in alanine aminotransferase or aspartate aminotransferase of >3 × ULN occurred in 3 patients with cirrhosis.

Conclusions

Seladelpar reduced biomarkers of cholestasis and was overall safe and well tolerated in patients with PBC with or without cirrhosis.

Conflict of interest: Yes, Gilead Sciences, Inc.