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Seladelpar improves liver stiffness in PBC: ASSURE interim analysis
Christopher L Bowlus1, Gideon M Hirschfield2, Alejandra M Villamil3
1Division of Gastroenterology and Hepatology, University of California Davis School of Medicine, Sacramento, CA, USA.
Background & Aims:
Liver stiffness measurement (LSM) by transient elastography can predict clinical outcomes in patients with primary biliary cholangitis (PBC), with ongoing disease activity associated with progressive LSM increases. Seladelpar is a first-in-class approved delpar with demonstrable biochemical and symptom improvements in PBC. We assessed LSM changes, with up to 3 years of seladelpar treatment, in an interim analysis of the ongoing, open-label ASSURE study.
Methods:
Patients with PBC rolled over into ASSURE from the pivotal, placebo-controlled RESPONSE study or enrolled after participation in earlier legacy studies. Patients who received seladelpar 10 mg with ≥1 on-treatment LSM were evaluated (cutoff: January 31, 2025). Patients were grouped by baseline LSM (kPa) into low (<10.7), intermediate (≥10.7 to <16.9), and high (≥16.9) risk. LSM change from baseline (CfB) was evaluated overall and by baseline risk category, with category shifts assessed at Month (M)36. Multivariate analysis identified factors associated with stable/improved versus worsening LSM at M36.
Results:
A total of 307 patients were included, with baseline mean (SD) LSM (kPa) of 9.8 (7.4); 72.6% were low-, 16.6% were intermediate-, and 10.7% were high-risk. Among 113 patients with M36 LSMs, median CfB was -3.4% overall and -29.7% among high-risk patients. Most patients (89/113; 78.8%) had stable/improved LSM at M36. Biochemical response at M12 was significantly associated with LSM stability/improvement at M36 (odds ratio [95% CI]: 4.30 [1.35, 13.71] for alkaline phosphatase [ALP] normalization and 4.21 [1.27, 13.92] for ALP >ULN but <1.67× ULN, versus ALP ≥1.67× ULN).
Conclusions:
Most patients with M36 LSMs available showed stable/improved liver stiffness with seladelpar treatment, with reductions observed among high-risk patients. Maintenance or improvement of liver stiffness was associated with biochemical response.
Clinical Trial Number:
NCT03301506 IMPACT AND IMPLICATIONS: Liver stiffness assessed by transient elastography is a prognostic tool reflecting risk of disease progression in patients with PBC. Among patients with baseline liver stiffness (FibroScan®) ≥10 kPa, those with cirrhosis, and those who do not receive adequate treatment, LSM has been observed to increase over time. This interim analysis suggests that long-term treatment with seladelpar, an approved second-line therapy, may lead to stable or improved LSM, with biochemical response associated with LSM stability and improvement. These results build on existing evidence of the efficacy of seladelpar, suggesting its potential to favorably impact disease progression. The results also highlight the importance of ALP reduction to reduce risk of disease progression in patients with PBC.
