2012年12月24日，美国食品药品管理局(FDA)已批准了Juxtapid(lomitapide)作为低脂饮食和其他降血脂治疗的辅助药物，用于降低纯合子家族性高胆固醇血症(HoFH)患者低密度脂蛋白胆固醇(LDL-C)、总胆固醇、载脂蛋白B和非高密度脂蛋白胆固醇(非-HDL)。Juxtapid是一种微粒体甘油三酯转运蛋白抑制剂。
FDA批准Juxtapid是基于一项关键性3期研究结果。该研究评价了29例HoFH患者服用Juxtapid降低LDL-C水平的有效性和安全性，是一项为期78周的国际多中心、单组、开放性研究，其结果发表于《柳叶刀》杂志。在这项研究中，Juxtapid初始治疗剂量为每天5 mg，基于耐受性和可接受的肝酶水平，剂量逐渐增加至10 mg、20 mg、40 mg和60 mg。
在现有降血脂治疗的Juxtapid添加治疗中，意向治疗患者平均LDL-C水平由基线时的336 mg/dL显著降至26周时的190 mg/dl(降低40%)，其中提前终止治疗患者采取末期观察推进法评估。23例完成26周研究患者LDL-C水平平均降低50%。在26周后的安全性评价阶段，允许调整同期降脂治疗。在长期治疗阶段，LDL-C平均降低幅度仍能维持。
该研究最常见不良反应是胃肠道反应，在29例患者中有27例(93%)报告出现胃肠道反应。28%的患者报告的不良反应包括腹泻、恶心、呕吐、消化不良和腹痛。其他常见不良反应有体重下降、腹部不适、腹胀、便秘、胃肠气胀、胸痛、流感、鼻咽炎和疲乏。还观察到肝酶水平和肝脏脂肪升高。
由于肝脏毒性风险，根据风险评估和降低策略，Juxtapid的使用将受到限制。在治疗开始之前，应检测肝脏转氨酶、碱性磷酸酶和总胆红素水平，并应定期监测丙氨酸转氨酶(ALT)和天冬氨酸转氨酶(AST)。治疗期间，如果ALT或AST水平≥3倍正常值最高上限，应调整Juxtapid剂量。一旦出现有临床意义的肝脏毒性，应停止使用Juxtapid。
考虑到Juxtapid作用于小肠，可能会减少脂溶性营养成分的吸收。接受Juxtapid治疗的患者应每天服用含有400 IU的维生素E和至少200 mg亚油酸、210 mgα-亚麻酸、110 mg EPA以及80 mg DHA的补充剂。
Juxtapid用于非HoFH高脂血症患者的安全性和有效性尚未确定。

Juxtapid Approved for Homozygous Familial Hypercholesterolemia

Aegerion Pharmaceuticals announced that the FDA has approved Juxtapid (lomitapide capsules) as an adjunct to a low-fat diet and other lipid-lowering treatments, including LDL apheresis where available, to reduce low-density lipoprotein cholesterol (LDL-C), total cholesterol, apolipoprotein B and non- high-density-lipoprotein cholesterol in patients with homozygous familial hypercholesterolemia (HoFH). Lomitapide is a MTP-inhibitor that reduces blood levels of cholesterol and triglyceride by limiting the production of lipoproteins from the intestine and liver.
The approval of Juxtapid was based on a multinational, single-arm, open-label, 78-week Phase 3 study, which eva luated the safety and effectiveness of the medicine to reduce LDL-C levels in 29 adult patients with HoFH. When added to the patients' existing lipid-lowering therapy, Juxtapid significantly reduced LDL-C by 40% at Week 26 in the intent-to-treat population with last observation carried forward for the patients who discontinued prematurely. LDL-C was reduced by an average of 50% for the 23 patients who completed the study through Week 26.
Because of the risk of liver toxicity, Juxtapid is available only through a restricted program called the Juxtapid Risk eva luation and Mitigation Strategy (REMS) Program. Aegerion will certify all health care providers who prescribe Juxtapid and the pharmacies that will dispense the medicine.