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

10-9-2024

Publication Title

Hepatology

Abstract

Background: Seladelpar, a novel delpar (selective PPARdelta agonist), is in development for the treatment of primary biliary cholangitis (PBC). The phase 3, placebocontrolled RESPONSE study (NCT04620733) in PBC patients with an inadequate response or intolerance to ursodeoxycholic acid demonstrated significant improvements in cholestatic markers and pruritus with seladelpar over one year. Similar proportions of seladelpar and placebo-treated patients experienced adverse events (AEs) and serious AEs (SAEs). 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 openlabel 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 subject incidences of AEs, SAEs, and AEs of interest (defined as liver-, muscle-, renal-, and pancreatic-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, 10 ≥5 years. The exposure-adjusted subject 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. There were no treatment-related SAEs. Muscle, renal, and pancreatic 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 subject 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 patientyears in seladelpar patients and 5.6 per 100 patient-years in placebo patients. Conclusion: 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

80

First Page

S1823

Last Page

S1824

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