LONG-TERM SAFETY OF SELADELPAR 10 MG WITH UP TO 5 YEARS OF TREATMENT IN PATIENTS WITH PRIMARY BILIARY CHOLANGITIS

Document Type

Conference Proceeding

Publication Date

6-23-2025

Publication Title

Gut

Abstract

Introduction The Phase 3, placebo-controlled RESPONSE study (NCT04620733) of seladelpar, a first-in-class delpar (selective PPAR-delta agonist), in primary biliary cholangitis (PBC) patients with an inadequate response or intolerance to ursodeoxycholic acid demonstrated significant improvements in cholestatic markers and pruritus with seladelpar over 1 year and similar proportions of adverse events (AEs) and serious AEs (SAEs) between the seladelpar and placebo groups. To assess long-term safety, data from all PBC patients exposed to seladelpar 10 mg in 6 studies with similar entry criteria were pooled. Methods AE data from 2 placebo-controlled and 4 open-label studies were pooled for all patients treated with seladelpar 10 mg as of 31 Jan 2024, beginning with first exposure to seladelpar, including all exposure periods and excluding treatment gaps. Placebo exposure was pooled from the 2 placebo-controlled studies. Exposure-adjusted patient incidences of AEs, SAEs, and AEs of interest (defined as liver-, muscle-, and renal-related AEs) were calculated. Results As of the data cutoff, a total of 486 patients received seladelpar 10 mg: 355 were treated for ≥1 year; 170, ≥2 years; 66, ≥3 years; 36, ≥4 years; and 10, ≥5 years. The exposure-adjusted patient incidence (per 100 patient-years) for seladelpar 10 mg was 48.3 for AEs, 8.0 for SAEs, 9.8 for Grade ≥3 AEs, and 6.1 for liver-related AEs (table 1). There were no treatment-related SAEs. Muscle and renal AEs occurred in <7 patients per 100 patient-years. Placebo exposure included 152 patients: 117 were treated for ≥12 weeks, 84 for ≥6 months, and 57 for 12 months of placebo treatment in RESPONSE. The exposure-adjusted patient incidence (per 100 patient-years) for patients treated with placebo was 132 for AEs (rate reflective of shorter exposure time for placebo patients), 7.8 for SAEs, 12.2 for Grade ≥3 AEs, and 13.3 for liver-related AEs (with other AEs of interest occurring at lower rates). AEs leading to treatment discontinuation occurred in 2.9 patients per 100 patient-years in seladelpar patients and 5.6 per 100 patient-years in placebo patients. Conclusions Analysis of a large safety database for seladelpar in PBC patients with exposure through 5 years indicated that seladelpar was well tolerated with a safety profile similar to placebo.

Volume

74

First Page

A228

Find It @ Sladen

Share

COinS