Long-Term Efficacy and Safety of Open-Label Seladelpar Treatment in Patients With Primary Biliary Cholangitis: Pooled Interim Results for Up to 3 Years From the ASSURE Study

The ongoing open-label phase 3 ASSURE trial is evaluating the long-term efficacy and safety of seladelpar 10 mg in patients with PBC who had received seladelpar in the placebo-controlled RESPONSE trial or in other earlier seladelpar trials.¹

A total of 337 patients have been enrolled in the ASSURE study, including 179 patients from legacy studies, 104 patients from the seladelpar arm of the RESPONSE trial, and 54 patients from the placebo arm of the RESPONSE trial. As of the data cutoff, 124 patients had at least 24 months of seladelpar exposure. The mean age of patients at baseline was 58.1 years; 94% of patients were female and 16% had cirrhosis.

Interim results reported by Lawitz and colleagues show that the composite biochemical response endpoint (defined as an ALP <1.67 x ULN, an ALP decrease >15%, and a normal total bilirubin level) was met in 73% of patients at month 12, 73% of patients at week 24, and 81% of patients at month 30 (Figure 5). The ALP normalization rate at month 30 was 41% (15 of 37). At month 30, ALT had normalized in 90% (17 of 19) of patients with elevated ALT at baseline. Among 37 patients with month 30 data, the mean percentage change from baseline in ALT, total bilirubin, and GGT was -29%, -5%, and -42%, respectively. Among 99 patients with moderate to severe pruritus at baseline, the mean change in pruritus NRS from baseline

Figure 5.

Composite biochemical response, a key efficacy endpoint, in patients with primary biliary cholangitis treated with seladelpar in the ASSURE study was met in 73% (204/280), 73% (90/124), and 81% (30/37) of patients at months 12, 24, and 30. Adapted from Lawitz EJ, et al. AASLD abstract 5044. Presented at: The Liver Meeting; November 15-19, 2024; San Diego, CA.¹

No new safety issues or changes in AE frequency were observed after up to 3 years of treatment. The most common AEs were COVID-19, pruritus, and nausea; most AEs of interest were grade 1 or 2 in severity. No serious treatment-related AEs were reported. One death caused by autoimmune hemolytic anemia was considered unrelated to seladelpar use. Rates of exposure-adjusted liver, muscle, and renal AEs were stable or decreased over the 3-year period.

The risk-benefit ratio for a treatment is important to all health care professionals, and data beyond the year 1 data used for licensing are an essential part of a clinician’s assessment of the treatment risk-benefit ratio. As demonstrated in this interim analysis of the ASSURE study, which included patients with PBC who participated in prior clinical seladelpar studies, the 3 years of safety and efficacy data provide a marked increase in confidence for seladelpar use.

— Robert G. Gish, MD