The phase 3 RESPONSE trial, presented at the AASLD Liver Meeting, showed that seladelpar, a novel selective peroxisome proliferator-activated receptor agonist, can reduce biomarkers of cholestasis and liver injury in patients with primary biliary cholangitis (PBC) with and without cirrhosis.
The study enrolled 193 patients with PBC who had:
- Inadequate response or intolerance to ursodeoxycholic acid;
- Alkaline phosphatase (ALP) at least 1.67 times the upper limit of normal (ULN); and
- Total bilirubin (TB) 2 or less times the ULN.
Patients were randomized 2:1 to receive daily oral seladelpar 10 mg or placebo for 12 months.
Of the cohort, 27 patients (14%) had Child-Pugh A compensated cirrhosis at baseline; 18 received seladelpar, and 9 received a placebo. Patients with cirrhosis had higher mean liver stiffness (18.8 vs 7.9 kPa), ALP (345.8 vs 309.2 U/L), and TB (0.97 vs 0.72 mg/dL) at baseline compared with those without cirrhosis.
After 12 months of treatment, the mean change in ALP from baseline in the cirrhosis group was –121.4 U/L with seladelpar versus 23.2 U/L with placebo. The mean change in the noncirrhotic group was –134.8 U/L versus –18.0 U/L, respectively.
The seladelpar group had greater numerical declines in gamma-glutamyl transferase and alanine aminotransferase (ALT) regardless of cirrhosis status.
Adverse events were similar between treatment groups and in patients with or without cirrhosis. No patients in the cirrhosis group discontinued seladelpar due to adverse events. In the cirrhosis group, 1 (5.6%) patient receiving seladelpar and 2 (22.2%) receiving placebo experienced elevated ALT or aspartate aminotransferase of more than 3 times the ULN.
“Seladelpar was overall safe and well tolerated in patients with and without cirrhosis,” the authors concluded.
Reference
Villamil A, Younes Z, Bowlus C, et al. Efficacy and safety of seladelpar in patients with primary biliary cholangitis and compensated cirrhosis in the phase 3 placebo-controlled RESPONSE trial. Abstract 0164. Presented at the 2024 American Association for the Study of Liver Diseases’ 75th Liver Meeting; November 15–19, 2024; San Diego.
