Open-label, clinical trial extension: Two-year safety and efficacy results of seladelpar in patients with primary biliary cholangitis
Recommended Citation
Mayo MJ, Vierling JM, Bowlus CL, Levy C, Hirschfield GM, Neff GW, Galambos MR, Gordon SC, Borg BB, Harrison SA, Thuluvath PJ, Goel A, Shiffman ML, Swain MG, Jones DEJ, Trivedi P, Kremer AE, Aspinall RJ, Sheridan DA, Dörffel Y, Yang K, Choi YJ, and McWherter CA. Open-label, clinical trial extension: Two-year safety and efficacy results of seladelpar in patients with primary biliary cholangitis. Aliment Pharmacol Ther 2023.
Document Type
Article
Publication Date
1-1-2024
Publication Title
Alimentary pharmacology & therapeutics
Abstract
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 and anti-pruritic effects.
AIMS: To evaluate the long-term safety and efficacy of seladelpar in patients with PBC.
METHODS: In an open-label, international, long-term extension study, patients with PBC completing seladelpar lead-in studies continued treatment. Seladelpar was taken orally once daily at doses of 5 or 10 mg with dose adjustment permitted for safety or tolerability. The primary analysis was for safety and the secondary efficacy analysis examined biochemical markers of cholestasis and liver injury. The study was terminated early due to the unexpected histological findings in a concurrent study for non-alcoholic steatohepatitis, which were subsequently found to predate treatment. Safety and efficacy data were analysed through 2 years.
RESULTS: There were no serious treatment-related adverse events observed among 106 patients treated with seladelpar for up to 2 years. There were four discontinuations for safety, one possibly related to seladelpar. Among 53 patients who completed 2 years of seladelpar, response rates increased from years 1 to 2 for the composite endpoint (alkaline phosphatase [ALP] <1.67 × ULN, ≥15% decrease in ALP, and total bilirubin ≤ULN) and ALP normalisation from 66% to 79% and from 26% to 42%, respectively. In those with elevated bilirubin at baseline, 43% achieved normalisation at year 2.
CONCLUSIONS: Seladelpar was safe, and markedly improved biochemical markers of cholestasis and liver injury in patients with PBC. These effects were maintained or improved throughout the second year.
CLINICALTRIALS: gov: NCT03301506; Clinicaltrialsregister.eu: 2017-003910-16.
Medical Subject Headings
Humans; Ursodeoxycholic Acid; Liver Cirrhosis, Biliary; Cholestasis; Biomarkers; Alkaline Phosphatase; Bilirubin
PubMed ID
37904314
ePublication
ePub ahead of print
Volume
59
Issue
2
First Page
186
Last Page
200
