原发性胆汁胆管炎新药奥贝胆酸OCALIVA(OBETICHOLIC ACID，一种鹅脱氧胆酸衍生物)TABLET ORAL获准上市，将成为近20年来获批治疗PBC的首个新药 5月27日，美国FDA加速批准Ocaliva(obeticholic acid,OCA)联合熊去氧胆酸(UDCA)用于UDCA单药治疗应答不佳的原发性胆汁性胆管炎(PBC)成人患者，或单药用于无法耐受UDCA的PBC成人患者。 原发性胆汁性胆管炎(PBC)是一种肝内胆小管渐进性损伤的慢性疾病，主要是因胆管遭到自身免疫性破坏，导致胆汁淤积。它主要影响女性，目前是美国女性进行肝脏移植手术的第二大病因。在欧洲，该病约占胆汁淤积性疾病所致肝移植病例的一半左右，约占所有肝移植病例的6%。 UDCA是目前唯一获批治疗PBC的药物。UDCA可有效治疗超过50%的患者。然而，多达40%的患者的ALP水平或总胆红素不会降低，且5%～10%的患者无法耐受UDCA。 FDA曾授予Ocaliva优先审查资格。OCA是一种法尼酯X受体激动剂，可促进胆汁酸的释放，开发用于原发性胆汁性肝硬化、非酒精性脂肪性肝炎及其他肝脏疾病和肠道疾病的治疗。此前，FDA已授予OCA治疗伴有肝纤维化的NASH的突破性药物资格、治疗PBC的快车道地位、治疗PBC和PSC的孤儿药地位。 FDA此次批准表明，Ocaliva能有效降低PBC患者的碱性磷酸酶(ALP)水平，并最终可以改善无移植生存率。 “未经治疗或UDCA治疗应答不佳的患者存在发生肝衰竭和死亡的风险，”FDA药物评价和研究中心主任Amy Egan博士指出，“Ocaliva的获批为UDCA治疗应答不佳的患者提供了一种重要的治疗选择。” Ocaliva的疗效和安全性监管文件的提交基于一项纳入了216例PBC患者的临床试验。研究显示，相比于对照组，Ocaliva治疗一年后患者的ALP水平降低。常见的不良事件为皮肤瘙痒、疲劳、腹部疼痛和不适、关节痛、头晕和便秘。根据FDA，Ocaliva不适用于肠道完全梗阻的患者。 POISE临床试验的研究数据显示，Ocaliva初始剂量5 mg，基于临床反应，治疗6个月时逐渐滴定至10mg，有助于降低患者皮肤瘙痒的严重程度和发生率。 “ Ocaliva满足了UDCA治疗应答不佳或无法耐受UDCA的患者的需求。” 贝勒医学院John Vierling教授在一项新闻稿中说到。 PBC组织主席Linie Moore指出，“PBC影响了个体的黄金时期，对一些人来说，还需要考虑进行肝移植。UDCA批准近20年后，我们终于迎来了治疗PBC个体的新型药物。” Ocaliva(Obeticholic Acid Tablets) General Information Ocaliva (obeticholic acid) is a farnesoid X receptor (FXR) agonist. Ocaliva is specifically indicated for the treatment of primary biliary cholangitis (PBC) in combination with ursodeoxycholic acid (UDCA) in adults with an inadequate response to UDCA, or as monotherapy in adults unable to tolerate UDCA. Ocaliva is supplied as tablets for oral administration. The recommended starting dosage of Ocaliva is 5 mg orally once daily in adult patients who have not achieved an adequate biochemical response to an appropriate dosage of UDCA for at least 1 year or are intolerant to UDCA. Dosage Titration: If an adequate reduction in ALP and/or total bilirubin has not been achieved after 3 months of Ocaliva 5 mg once daily, and the patient is tolerating Ocaliva, increase the dosage of Ocaliva to 10 mg once daily. The maximum recommended dosage of Ocaliva is 10 mg once daily. Please see drug label for specific dose adjustments. Mechanism of Action Ocaliva (obeticholic acid) is a farnesoid X receptor (FXR) agonist. FXR is a nuclear receptor expressed in the liver and intestine. FXR is a key regulator of bile acid, inflammatory, fibrotic, and metabolic pathways. FXR activation decreases the intracellular hepatocyte concentrations of bile acids by suppressing de novo synthesis from cholesterol as well as by increased transport of bile acids out of the hepatocytes. These mechanisms limit the overall size of the circulating bile acid pool while promoting choleresis, thus reducing hepatic exposure to bile acids. OCALIVA Rx Generic Name and Formulations: Obeticholic acid 5mg, 10mg; tabs. Company: Intercept Pharmaceuticals Indications for OCALIVA: Treatment of primary biliary cholangitis in combination with ursodeoxycholic acid (UDCA) in adults with inadequate response to UDCA, or as monotherapy in adults unable to tolerate UDCA. Adult: Initially 5mg once daily. Increase to 10mg once daily if inadequate reduction in ALP and/or total bilirubin after 3 months and tolerated the drug; max 10mg once daily. Moderate or severe hepatic impairment: initially 5mg once weekly; increase to 5mg twice weekly (≥3 days apart) then to 10mg twice weekly (≥3 days apart) if inadequate reduction in ALP and/or total bilirubin after 3 months and tolerated the drug. Intolerable pruritus: consider adding an antihistamine or bile acid binding resin; or reducing dose to 5mg every other day (if intolerant to 5mg daily) or 5mg once daily (if intolerant to 10mg daily); or temporarily interrupt for up to 2 weeks then restart at lower dose. Increase dose to 10mg once daily as tolerated for optimal response. Children: Not established. Contraindications: Complete biliary obstruction. Warnings/Precautions: Discontinue if intolerable pruritus persists or complete biliary obstruction develops. Monitor for elevations in liver biochemical tests and liver-related adverse effects. Monitor for changes in serum lipid levels. If unresponsive after 1 year of treatment at max tolerable dose (10mg once daily) and experienced HDL-C reduction, reevaluate. Pregnancy. Nursing mothers. Interactions: Separate dosing by ≥4hrs or at greatest possible interval with bile acid binding resins (eg, cholestyramine, colestipol, colesevelam). Concomitant warfarin: monitor INR and adjust dose as needed. Concomitant CYP1A2 substrates with narrow therapeutic index (eg, theophylline, tizanidine); monitor. Pharmacological Class: Farnesoid X receptor (FXR) agonist. Adverse Reactions: Pruritus, fatigue, abdominal pain/discomfort, rash, oropharyngeal pain, dizziness, constipation, arthralgia, thyroid function abnormality, eczema; liver-related effects, HDL-C reduction. Generic Availability: NO How Supplied: Tabs—30 完整资料附件：https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=cdfbe0cd-eb15-45a1-ac17-531bcda21aec -------------------------------------------------- 产地国家： 美国  原产地英文商品名: Ocaliva tabs 5mg/tablet 30tablets/bottle 原产地英文药品名: obeticholic acid 中文参考商品译名: Ocaliva片 5毫克/片 30片/瓶 中文参考药品译名: 奥贝胆酸 生产厂家中文参考译名: Intercept Pharmaceuticals, Inc 生产厂家英文名: Intercept Pharmaceuticals, Inc   -------------------------------------------------- 产地国家： 美国  原产地英文商品名: Ocaliva tabs 10mg/tablet 30tablets/bottle 原产地英文药品名: obeticholic acid 中文参考商品译名: Ocaliva片 10毫克/片 30片/瓶 中文参考药品译名: 奥贝胆酸 生产厂家中文参考译名: Intercept Pharmaceuticals, Inc 生产厂家英文名: Intercept Pharmaceuticals, Inc