Treatment with seladelpar for up to 2 years improves cholestatic biomarkers and pruritus in patients with primary biliary cholangitis (PBC), with no serious safety concerns noted with long-term use, as shown by interim results of the ASSURE study.
“[T]hese interim results demonstrated a durable effect on biochemical markers of PBC with seladelpar treatment up to 2 years, consistent with the significant improvements in disease markers observed in the phase 3, placebo-controlled RESPONSE study,” the investigators said. “The significant effect on pruritus seen in RESPONSE was sustained during the additional 6-month evaluation period in ASSURE.”
At interim cutoff, 337 patients from the RESPONSE study or with previous participation in earlier legacy studies were enrolled and treated with at least one seladelpar 10-mg dose: 54 placebo-treated and 104 seladelpar-treated from RESPONSE and 179 from legacy studies.
The investigators conducted interim evaluations, including composite biochemical response (alkaline phosphatase <1.67 upper limit of normal, total bilirubin ≤ upper limit of normal, and alkaline phosphatase decrease ≥15 percent), pruritus numerical rating scale (NRS) change among patients with a baseline score ≥4, and safety.
At RESPONSE completion, the composite response rate was significantly higher with seladelpar than with placebo (62 percent [79/128] vs 20 percent [13/65]). [Am J Gastroenterol 2026;121:1140-1153]
Among patients who rolled over from RESPONSE, the response rates after 12 months in ASSURE were 72 percent (21/29) in participants continuing seladelpar use and 94 percent (15/16) in crossover seladelpar patients. In legacy trial, the response rates among patients were 73 percent (120/164) after 12 months of treatment in ASSURE and 70 percent (69/99) after 24 months.
The decrease in NRS at RESPONSE completion persisted in seladelpar-treated patients with baseline NRS ≥4 (‒3.4) after 6 additional months of treatment (‒3.8). Similar changes were observed in crossover seladelpar (‒3.8) and legacy patients (‒3.5) after 6 months of treatment in ASSURE.
Serious adverse events associated with seladelpar did not occur.
“No new safety signals were identified among patients treated with seladelpar beyond 2 years,” the investigators said. “These interim data support seladelpar as an effective and safe long-term PBC treatment in patients who have had an inadequate response or intolerance to ursodeoxycholic acid.”
Mechanism
The exact mechanism by which seladelpar improves pruritus remains unknown, but a previous study found that such improvement is associated with reductions in bile acids and the pruritogenic cytokine interleukin-31. [Hepatology 2024;80:27-37]
Specifically, bile acids and interleukin-31 levels at baseline were increased in patients with pruritus related to PBC and were reduced in those treated with seladelpar and demonstrated pruritus improvement.
“Due to the ongoing nature of ASSURE, not all patients have reached later time points, and follow-up time for RESPONSE rollover patients was more limited than for legacy patients,” the investigators said. “Longer term data from this ongoing study will continue to be informative, although this analysis does provide important insight into safety with extended treatment based on available follow-up time.”
PBC, a rare, autoimmune, chronic liver disease, can lead to cirrhosis and liver failure, and some of its symptoms include pruritus and fatigue, which can affect quality of life. [J Clin Transl Hepatol 2020;8:49-60; J Clin Transl Hepatol 2020;8:49-60]