Seladelpar in patients with primary biliary cholangitis and compensated cirrhosis: Efficacy and safety from RESPONSE and ASSURE studies.

IF 6 2区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY

Hepatology Communications Pub Date : 2026-04-13 eCollection Date: 2026-05-01 DOI:10.1097/HC9.0000000000000918

Stuart C Gordon, Alejandra Villamil, Ira M Jacobson, Eric J Lawitz, Ziad Younes, Marina G Silveira, Christopher L Bowlus, Joost P H Drenth, John M Vierling, Ulrike Morgera, Adam Vasura, George Dalekos, Andrea Galli, Mordechai Rabinovitz, Jeong Heo, Frederik Nevens, Cynthia Levy, Yan Zhou, Susheela Carroll, Daria B Crittenden

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引用次数: 0

Abstract

Background: Treatment options are limited for patients with primary biliary cholangitis (PBC) and cirrhosis. Seladelpar, a first-in-class delpar (selective PPAR-δ agonist), had generally similar efficacy and safety among patients with versus without compensated cirrhosis in the phase 3 RESPONSE study. Here we provide additional data on seladelpar in patients with compensated cirrhosis from the phase 3 program.

Methods: In RESPONSE, patients with PBC and an inadequate response or intolerance to UDCA were randomized 2:1 to seladelpar 10 mg or placebo for 1 year. Upon completion, patients rolled over into the open-label (seladelpar 10 mg) phase 3 ASSURE study, which also enrolled patients from earlier seladelpar legacy PBC studies. Here, we assessed the composite endpoint [alkaline phosphatase (ALP) <1.67×upper limit of normal (ULN), ALP decrease ≥15%, and total bilirubin ≤ULN], other laboratory changes, and safety in all patients with cirrhosis from RESPONSE and an interim analysis of the ongoing ASSURE study through January 2024.

Results: Twenty-seven patients with compensated cirrhosis enrolled in RESPONSE (18 seladelpar, 9 placebo). At month 12, 38.9% and 22.2% of patients in the seladelpar and placebo groups, respectively, met the composite endpoint; mean percent change from baseline in ALP was -37.1% and -10.1%, respectively. Upon rollover to ASSURE (13 seladelpar, 6 placebo), ALP declines were maintained for up to 18 months. An additional 35 patients with compensated cirrhosis in ASSURE from legacy studies had similar reductions in ALP with up to 2 years of treatment. Bilirubin remained overall stable. No treatment-related serious adverse events occurred. Variceal bleeding and/or ascites developed in 3 patients after ≥9 months.

Conclusions: Seladelpar decreased markers of cholestasis and was overall safe and well-tolerated in patients with PBC and compensated cirrhosis.

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Seladelpar对原发性胆道炎和代偿性肝硬化患者的疗效和安全性：来自RESPONSE和ASSURE研究。

背景：原发性胆道胆管炎（PBC）和肝硬化患者的治疗选择有限。Seladelpar是一种一流的delpar（选择性PPAR-δ激动剂），在3期应答研究中，在代偿性肝硬化患者与非代偿性肝硬化患者中具有普遍相似的疗效和安全性。在这里，我们提供了来自3期项目的seladelpar在代偿性肝硬化患者中的额外数据。方法：在RESPONSE中，对UDCA反应不足或不耐受的PBC患者按2:1随机分配至10 mg seladelpar或安慰剂组，为期1年。完成后，患者转入开放标签（seladelpar 10 mg） 3期ASSURE研究，该研究也纳入了早期seladelpar遗留PBC研究的患者。在这里，我们评估了复合终点[碱性磷酸酶（ALP）]结果：27例代偿性肝硬化患者参加了RESPONSE（18例seladelpar， 9例安慰剂）。在第12个月，塞拉德帕组和安慰剂组分别有38.9%和22.2%的患者达到了复合终点；与基线相比，ALP平均变化百分比分别为-37.1%和-10.1%。在转到ASSURE组（13例seladelpar， 6例安慰剂）后，ALP下降维持了长达18个月。在ASSURE研究中，另外35例代偿性肝硬化患者在长达2年的治疗后ALP也有类似的降低。胆红素总体保持稳定。未发生治疗相关的严重不良事件。3例患者在≥9个月后出现静脉曲张出血和/或腹水。结论：西拉得帕降低了胆汁淤积标志物，对PBC和代偿性肝硬化患者总体安全且耐受性良好。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Hepatology Communications GASTROENTEROLOGY & HEPATOLOGY-

CiteScore

8.00

自引率

2.00%

发文量

248

审稿时长

8 weeks

期刊介绍： Hepatology Communications is a peer-reviewed, online-only, open access journal for fast dissemination of high quality basic, translational, and clinical research in hepatology. Hepatology Communications maintains high standard and rigorous peer review. Because of its open access nature, authors retain the copyright to their works, all articles are immediately available and free to read and share, and it is fully compliant with funder and institutional mandates. The journal is committed to fast publication and author satisfaction.