Open‐label, clinical trial extension: Two‐year safety and efficacy results of seladelpar in patients with primary biliary cholangitis

• DOI: 10.1111/apt.17755
• Publication Date: 2023-10-31T04:55:25Z
• Authors: Marlyn J. Mayo; John M. Vierling; Christopher L. Bo...; Cynthia Levy; Gideon M. Hirschf...; Guy W. Neff; Michael R. Galambos; Stuart C. Gordon; Brian B. Borg; Stephen A. Harrison; Paul J. Thuluvath; Aparna Goel; Mitchell L. Shiffman; Mark G. Swain; David E. J. Jones; Palak Trivedi; Andreas E. Kremer; Richard J. Aspinall; David A. Sheridan; Yvonne Dörffel; Ke Yang; Yun‐Jung Choi; Charles A. McWherter
• Keywords: Tolerability; Clinical endpoint; Primary Biliary Cirrhosis; Ursodeoxycholic acid; Steatohepatitis

Summary Background Seladelpar is a potent and selective peroxisome proliferator‐activated receptor‐δ agonist that targets multiple cell types involved in primary biliary cholangitis (PBC), leading to anti‐cholestatic, anti‐inflammatory anti‐pruritic effects. Aims To evaluate the long‐term safety efficacy of seladelpar patients with PBC. Methods In an open‐label, international, extension study, PBC completing lead‐in studies continued treatment. was taken orally once daily at doses 5 or 10 mg dose adjustment permitted for tolerability. The analysis secondary examined biochemical markers cholestasis liver injury. study terminated early due unexpected histological findings concurrent non‐alcoholic steatohepatitis, which were subsequently found predate Safety data analysed through 2 years. Results There no serious treatment‐related adverse events observed among 106 treated up four discontinuations safety, one possibly related seladelpar. Among 53 who completed years seladelpar, response rates increased from 1 composite endpoint (alkaline phosphatase [ALP] <1.67 × ULN, ≥15% decrease ALP, total bilirubin ≤ULN) ALP normalisation 66% 79% 26% 42%, respectively. those elevated baseline, 43% achieved year 2. Conclusions safe, markedly improved injury These effects maintained throughout second year. Clinicaltrials.gov: NCT03301506; Clinicaltrialsregister.eu: 2017‐003910‐16.