Background: Seladelpar, a potent and selective PPAR-delta agonist, has anti-cholestatic and anti-pruritic activity in patients with primary biliary cholangitis (PBC). In the ongoing, international phase 3 ASSURE study (NCT03301506), patients with prior participation in seladelpar PBC studies receive open-label seladelpar. Here we report interim efficacy and safety results from ASSURE for subjects who had previously participated in a study of seladelpar in PBC.

Methods: Patients with PBC were eligible if they had an inadequate response or intolerance to ursodeoxycholic acid (UDCA) and previously participated in a seladelpar PBC study. All patients received open-label seladelpar 10 mg oral daily. As of the data cutoff (29 June 2023), 174 patients were enrolled having previously participated in a seladelpar study (CB8025-21629, NCT02955602; CB8025-31731, NCT03301506; ENHANCE, NCT03602560; CB8025-21838, NCT04950764), the majority of which had a gap of > 1 year off treatment. Biochemical endpoints included a composite response of ALP < 1.67xULN, ALP decrease ≥ 15% and TB ≤ ULN; ALP normalization; and changes from baseline in ALP, GGT, ALT, and TB through Month 12.

Results: Of the 174 patients, most were female (94%) with a mean age of 58.6 ± 9.56 years. Key baseline characteristics were mean ALP 270.5 U/L and TB 0.75 mg/dL (13.8% > ULN) (1A). The majority (168/174, 96.6%) of patients were concurrently treated with UDCA and 33 (19%) had cirrhosis.

As of the data cut, 148 (85%) patients had reached 12 months of treatment. 70.3% of patients achieved the composite response endpoint with seladelpar 10 mg (1B). ALP normalization occurred in 37.2% of those receiving seladelpar (1C). The mean ALP % change from baseline was -44.4% (-144.4 U/L) (1D). Seladelpar lowered GGT, ALT, and TB by 36.4%, 25.2%, and 9.2% from baseline, respectively. There were no treatment-related serious adverse events. Discontinuation from treatment due to adverse events occurred in 4.0% of patients.

Conclusions: In this open-label phase 3 study, seladelpar led to clinically meaningful improvements in markers of cholestasis and liver injury, including high rates of ALP normalization. Seladelpar appeared overall safe and well tolerated through Month 12. The long-term safety and efficacy of seladelpar continues to be evaluated in the ongoing ASSURE study.

Charles Mcwherter

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