Ursodiol

吉利德科学公司（Gilead Sciences）日前宣布，欧盟委员会（EC）已有条件批准seladelpar上市，与熊去氧胆酸（UDCA）联用，治疗对UDCA单药应答不足的原发性胆汁性胆管炎（PBC）患者。或作为单药，用于对UDCA治疗不耐受的PBC患者。 PBC是一种罕见的慢性自身免疫性胆管疾病，在女性中更为常见，并会导致肝损伤，若不治疗，可能进展为可致命的肝功能衰竭。PBC最常见的症状为瘙痒和疲劳，目前尚无治愈PBC的方法，治疗目标包括减缓疾病进展以及减轻与胆汁淤积相关的症状，如胆汁性瘙痒。治疗效果主要通过改善肝脏生化指标来衡量，其中包括碱性磷酸酶（ALP）水平的正常化，这是PBC疾病进展的重要指标。 EU的批准主要依据关键性3期临床试验RESPONSE的研究结果。在该研究中，62%接受seladelpar治疗的参与者在第12个月达到了综合生化应答这一主要终点，而安慰剂组这一数值仅为20%。接受seladelpar治疗的试验参与者中，有25%在第12个月实现了ALP值的正常化，而在接受安慰剂的参与者中未观察到此变化。第6个月与基线相比的瘙痒评分变化为另一个关键性次要终点，接受seladelpar治疗的患者显示出与安慰剂相比具有统计学显著性的瘙痒减轻。 Seladelpar是一种口服的强效选择性过氧化物酶体增殖物活化受体δ（PPARδ）激动剂。研究表明，PPARδ能够调节关键的代谢及肝病相关途径。临床前和临床数据表明，seladelpar具有抗胆汁淤积、抗炎、止痒及抗纤维化作用。该疗法原由CymaBay公司所研发，吉利德科学在2024年2月与该公司达成总额达43亿美元的收购协议，进而囊获这款疗法。 Seladelpar已于2024年8月获得美国FDA的加速批准（商品名Livdelzi），用于治疗PBC。Seladelpar曾获得FDA授予的突破性疗法认定以及针对PBC患者的孤儿药资格，以及欧洲药品管理局授予的PRIME资格。作为FDA加速批准的一部分，吉利德承诺进行一项名为AFFIRM的确认性长期结局研究，该研究已在代偿期肝硬化患者中启动。 参考资料： [1] Gilead’s Seladelpar Granted Conditional European Marketing Authorization for the Treatment of Primary Biliary Cholangitis. Retrieved February 21, 2025, from https://www.businesswire.com/news/home/20250213709259/en 内容来源于网络，如有侵权，请联系删除。

Gilead Sciences’ seladelpar has been granted conditional marketing authorisation by the European Commission (EC) to treat patients with the rare liver disease primary biliary cholangitis (PBC). The drug has been approved for use in combination with ursodeoxycholic acid (UDCA) to treat adults who have an inadequate response to UDCA alone, and as a monotherapy for those who are unable to tolerate UDCA. Approximately 163,000 people in Europe are affected by PBC, an autoimmune disease of the bile ducts that disproportionally affects women. The disease usually develops very slowly over many years and is characterised by pruritus, or chronic itch, and fatigue. It can also cause liver damage and possible liver failure if left untreated. Seladelpar, an oral peroxisome proliferator-activated receptor-delta agonist, is designed to reduce the production of bile acid in the liver, preventing liver damage and reducing circulating bile acid levels. The EC’s decision follows a recent recommendation from the European Medicines Agency’s human medicines committee and was supported by positive results from the phase 3 RESPONSE study, in which 62% of patients receiving daily seladelpar achieved the primary endpoint of composite biochemical response at one year, compared to 20% of those on placebo. Seladelpar led to normalisation of alkaline phosphatase values, a cholestatic marker that is a predictor of risk for liver transplant and death, in 25% of patients at one year, while this change was not seen in any patients receiving placebo. Patients treated with Gilead’s drug also demonstrated a statistically significant reduction in pruritus compared to placebo. Timothy Watkins, vice president, clinical development of inflammation therapeutics at Gilead, said: “People living with PBC in Europe have been waiting for treatment advancements for many years. Up until now, there has been no approved treatment for PBC addressing both the surrogate biomarkers for underlying disease and pruritus, a common and at times debilitating symptom of PBC. “That changes… with the conditional approval of seladelpar, which has been shown to both help treat the disease and reduce pruritus.” Watkins added that the company is “[looking] forward to working with health authorities across Europe to bring this promising new treatment to all those who could benefit”. In line with the EC’s conditional approvals pathway, continued authorisation of seladelpar in these PBC indications will be contingent on the verification and description of clinical benefit.