Division of Gastroenterology and Hepatology, Henry Ford Health, Detroit, MI, USA.
School of Medicine, Michigan State University, E. Lansing, MI, USA.
Expert Opin Pharmacother. 2024 Aug;25(11):1517-1523. doi: 10.1080/14656566.2024.2390120. Epub 2024 Aug 11.
Seladelpar (MBX-8025) is a once-daily administered highly specific PPAR-δ agonist in Phase 3 and extension trials for use in patients with primary biliary cholangitis (PBC).
This review provides background on current treatment options for PBC, and summarizes clinical trial data regarding the safety and effectiveness of seladelpar within the context of these treatments.
Clinical trials results demonstrate the safety and tolerability of seladelpar use for PBC, including in patients with cirrhosis. The primary composite endpoint (ALP <1.67 times ULN, decrease ≥ 15% from baseline, and TB ≤ULN) was met in 61.7% of the patients treated with seladelpar and in 20% receiving placebo ( < 0.001). Moreover, pruritus - a cardinal and often intractable symptom of PBC - was improved with seladelpar treatment, as were overall quality of life measurements. Improvements in markers of inflammation were likewise observed. These biochemical and clinical findings therefore represent landmark developments in PBC treatment and offer a therapeutic option for PBC.
Seladelpar（MBX-8025）是一种每日一次给药的高度特异性过氧化物酶体增殖物激活受体 δ 激动剂，目前正在进行 3 期和扩展试验，用于原发性胆汁性胆管炎（PBC）患者。
本文提供了 PBC 当前治疗选择的背景信息，并在这些治疗方法的背景下总结了 seladelpar 安全性和有效性的临床试验数据。
临床试验结果表明，seladelpar 用于 PBC 的安全性和耐受性良好，包括在肝硬化患者中。61.7%接受 seladelpar 治疗的患者和 20%接受安慰剂治疗的患者达到了主要复合终点（碱性磷酸酶 <1.67 倍正常值上限，与基线相比下降 ≥15%，且总胆红素 ≤正常值上限）（<0.001）。此外，瘙痒（PBC 的一个主要且通常难以治疗的症状）得到了 seladelpar 治疗的改善，整体生活质量测量也得到了改善。炎症标志物也同样得到了改善。因此，这些生化和临床发现是 PBC 治疗的里程碑式进展，为 PBC 提供了一种治疗选择。
