CymaBay: Analysis of Phase 3 ENHANCE study published in Hepatology

CymaBay Therapeutics announced the first published findings demonstrating the impact of seladelpar on serum interleukin-31 levels and its correlation with pruritus improvement in people with primary biliary cholangitis. Seladelpar is a first-in-class oral, selective PPARdelta 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 today 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%, pless than0.0001) 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, pless than0.0001). 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, pless than0.0001) and conjugated bile acids (up to 0.64, pless than0.0001). Strong correlations were also observed between changes in IL-31 levels and changes in total bile acids (r=0.63, pless than0.0001) and conjugated bile acids in the seladelpar 10 mg group.