ENHANCE phase III study evaluating MBX 8025 in primary biliary cholangitis published in Hepatology.- CymaBay Therapeutics

CymaBay Therapeutics announced that results from the ENHANCE phase III global study evaluating MBX 8025 (seladelpar) for primary biliary cholangitis (PBC) have been published in Hepatology. his double-blind, placebo-controlled, global phase III study evaluated the efficacy and safety of seladelpar, a potent, selective, orally active PPAR? agonist, or delpar, after 3 months of treatment in patients with PBC. Patients with elevated alkaline phosphtase (at least 1.67x upper-limit-of-normal) received treatment as an add-on to first line ursodeoxycholic acid (UDCA), or as monotherapy, if patients were intolerant to UDCA. All pre-specified endpoints were assessed after 3 months in patients receiving oral daily seladelpar 5 mg (n=56), 10 mg (n=55) or placebo (n=56). The primary endpoint was a composite of alkaline phosphatase and bilirubin2 previously accepted by FDA for pivotal studies in PBC. The composite endpoint was achieved in 78.2% of patients on seladelpar 10 mg and 57.1% on seladelpar 5 mg versus 12.5% on placebo (both seladelpar doses with p<0.0001).>

A key secondary endpoint of having normal levels of alkaline phosphatase was met in 27.3% (p<0.0001) and 5.4 p="0.08)" in seladelpar 10 mg and 5 mg groups respectively versus none in the placebo group. the final key secondary endpoint assessed the patient-reported symptom of pruritus itching using a daily pruritus numerical rating scale nrs 0-10. statistically significant improvement in pruritus p><0.02) for patients with moderate-to severe itch nrs at least 4 was demonstrated for seladelpar 10 mg versus placebo. patients taking seladelpar also had significant improvements in markers of liver injury. there were no treatment related adverse endpoints in the study.>

See: "Seladelpar efficacy and safety at 3 months in patients with primary biliary cholangitis: ENHANCE, a phase 3, randomized, placebo-controlled study." Hirschfield, Gideon et al. Hepatology 10.1097/HEP.0000000000000395, April 6, 2023. DOI: 10.1097/HEP.0000000000000395