Oral Peroxisome Receptor Shows Benefit in Primary Biliary Cholangitis

The use of seladelpar can lead to a lasting potent anticholestatic effect among patients with primary biliary cholangitis (PBC) who were unresponsive or intolerant to ursodeoxycholic acid (UDCA), according to study findings. 

Seladelpar is a potent, selective peroxisome proliferator-activated receptor δ PPAR-delta agonist and a candidate therapy for inflammatory liver diseases.

In this ongoing phase 2 trial, Dr Christopher Bowlus from UC Davis Medical Center and colleagues randomly assigned participants to either 5 mg or 10 mg seladelpar for 52 weeks. If participants in the 5 mg seladelpar group did not meet the alkaline phosphatase goal, they could increase seladelpar to 10 mg. 

All participants had either an inadequate response to or were intolerant to UDCA, as well as had an alkaline phosphatase level at least 1.67 times the upper limit of normal.

Overall, 119 patients were exposed to at least 1 dose of seladelpar; each group had 17 patients complete the 52-week treatment.

The mean decrease in alkaline phosphatase from baseline was -47% in the 5/10 mg group and -46% in 10 mg group, which served as the study’s primary efficacy outcome. Further, 59% and 71% of participants in the 5/10 mg and 10 mg groups, respectively, responded to the composite efficacy.

After 1 year, 24% of participants in the 5/10 mg group and 29% of participants in the 10 mg group had normalized alkaline phosphatase levels.

Median alanine aminotransferase decreases were -31% in the 5/10 mg and -33% in the 10 mg groups, whereas median changes in the visual analog scale were -30% in the 5/10 mg and -66% in 10 mg groups.

“Seladelpar was generally safe, well tolerated, and not associated with pruritus,” the researchers concluded. “A 52-week phase 3 PBC study has been initiated to confirm these results.”

—Colleen Murphy

Reference:

Bowlus CL, Neff GW, Aspinall R, et al. Efficacy and safety of seladelpar, a selective peroxisome proliferator-activated receptor delta agonist, in primary biliary cholangitis: 52-week analysis of an ongoing international, randomized, dose ranging phase 2 study. Paper presented at: AASLD’s The Liver Meeting; November 9-13, 2018; San Francisco, CA. https://plan.core-apps.com/tristar_aasld18/abstract/1cd464b79336d9176dd9c2472ad41815. Accessed November 6, 2018.