CymaBay announces 'positive' results from seladelpar Phase 2 study
CymaBay announced positive interim results from its ongoing low-dose Phase 2 study of seladelpar in patients with primary biliary cholangitis, or PBC, a life-threatening and life-limiting chronic cholestatic liver disease. In the first part of the study, patients at high risk of disease progression, with an inadequate response to ursodeoxycholic acid, or UDCA, as characterized by a persistent elevation in alkaline phosphatase, or AP, or who were intolerant to UDCA, received either 5 mg or 10 mg of seladelpar once-daily. A planned interim analysis of the first 24 patients enrolled in these two dose groups demonstrated after 12 weeks of treatment a significant AP reduction from baseline of 39% and 45% for the 5 mg and 10 mg groups, respectively. On seladelpar, 45% of patients in the 5 mg and 82% of patients in the 10 mg dose groups had AP values less than 1.67 times the upper limit of normal, or ULN. AP is an established surrogate marker of disease progression in PBC, and reaching a level of less than 1.67 x ULN is a key component in the composite endpoint used for regulatory approval. Alongside substantial reductions in AP, patients in both dose groups experienced decreases in other liver markers of cholestasis including gamma glutamyl transferase and total bilirubin. Seladelpar also improved metabolic and inflammatory markers with patients experiencing decreases in low-density lipoprotein-C and high sensitivity C-reactive protein. There were no serious adverse events and no safety transaminase signal was observed at either dose. Instead, mean transaminase levels decreased over the course of treatment, further supporting seladelpar's anti-inflammatory activity. Consistent with prior studies, there was no signal for drug-induced pruritus. After sharing preliminary results from the study, the FDA has agreed to allow continuation of seladelpar treatment beyond six months for the 5 mg and 10 mg doses.