An analysis from the RESPONSE trial presented at the AASLD Liver Meeting showed that seladelpar reduced alkaline phosphatase (ALP) in several subgroups of patients with primary biliary cholangitis (PBC).
Previously reported results of the pivotal, phase 3, placebo-controlled trial showed that seladelpar, a novel selective PPAR agonist, improved composite biochemical response in patients with PBC. This report described additional ALP responses in this clinical trial.
The study included patients who received ursodeoxycholic acid (UDCA) for at least 12 months or were intolerant to UDCA and had ALP 1.67 or more times the upper limit of normal (ULN) and total bilirubin up to 2 times the ULN. The researchers randomized patients 2:1 to receive seladelpar 10 mg daily (n=128) or placebo (n=65). The researchers assessed ALP changes across demographic subgroups, baseline ALP quartiles, and in patients who did not meet the composite biochemical endpoint.
The mean baseline ALP was 314.6 U/L in the seladelpar group versus 313.8 U/L in the placebo group. At month 12, seladelpar reduced ALP similarly across all subgroups, including in patients with cirrhosis, aged less than 50 years at diagnosis, and of Hispanic/Latino ethnicity.
Among 53 patients (27.5%) with a baseline ALP 350 U/L and above, seladelpar led to a greater decrease (–44.8%; –216.1 U/L) in ALP compared with placebo (–11.6%; –56.4 U/L); this trend was also observed in patients with a baseline ALP of less than 350 U/L. Seladelpar reduced ALP similarly across baseline ALP quartiles.
Among those who did not meet the composite biochemical endpoint at month 12, ALP decreased by –129.9 U/L with seladelpar versus –6.4 U/L with placebo.
Seven (5.5%) patients treated with seladelpar and 19 (29.2%) treated with placebo experienced an increase in ALP from baseline to month 12.
Most patients experienced adverse events: 86.4% in the baseline ALP less than 350 U/L cohort and 84.9% in the baseline ALP 350 U/L and higher cohort, with a similar proportion of events occurring in both the seladelpar and placebo cohorts.
“Seladelpar led to robust and consistent ALP decreases across all subgroups studied,” the authors concluded.
Reference
Kowdley K, Yimam K, Kumar S, et al. Alkaline phosphatase changes with seladelpar across subgroups of primary biliary cholangitis patients in the RESPONSE trial. Abstract 4339. Presented at the 2024 American Association for the Study of Liver Diseases’ 75th Liver Meeting; November. 15–19, 2024; San Diego.
