CymaBay Therapeutics, Inc. announced the first published findings demonstrating the impact of seladelpar on serum interleukin-31 (IL-31) levels and its correlation with pruritus improvement in people with primary biliary cholangitis (PBC). Seladelpar is a first-in-class oral, selective PPARd agonist being investigated for the treatment of patients with PBC. The latest findings from a post-hoc analysis of the Phase 3 ENHANCE study, were published in the open access journal Hepatology and are the first peer-reviewed published report of a correlation in decreases in IL-31, bile acids and pruritus symptoms in PBC following treatment with an investigational agent.

In a post-hoc analysis of the Phase 3 ENHANCE study, IL-31 serum levels were measured in people with PBC who received daily oral doses of seladelpar 5 mg (n=53), 10 mg (n=53) or placebo (n=55) for three months. IL-31 is a cytokine known to mediate pruritus and blocking IL-31 signaling can provide relief in pruritic skin diseases. Statistically significant dose-dependent decreases in IL-31 were observed with seladelpar 5 mg (-30%, p=0.0003) and 10 mg (-52%, p<0.0001) compared to placebo (+31%) in the study.

IL-31 levels correlated with pruritus intensity using a numerical rating scale (NRS, 0-10; r=0.54, p<0.0001). Participants who experienced an improvement in pruritus (decrease in NRS of 2 or more) demonstrated greater dose-dependent reductions in IL-31 compared to those without pruritus improvement (decrease in NRS of less than 2). Baseline IL-31 levels also closely correlated with total (r=0.54, p<0.0001) and conjugated bile acids (up to 0.64, p<0.0001).

Strong correlations were also observed between changes in IL-31 levels and changes in total bile acids (r=0.63, p<0.0001) and conjugated bile acids in the seladelpar 10 mg group.