2014年2月24日，美国FDA批准Myalept（注射用美曲普汀）作为替代治疗药物结合饮食用于治疗先天性或获得性全身脂肪代谢障碍患者的瘦素缺乏并发症。

全身脂肪代谢障碍是一种与脂肪组织缺乏有关的病症。先天性全身脂肪代谢障碍患者出生时很少或根本没有脂肪组织。获得性全身脂肪代谢障碍患者通常随着时间的推移失去脂肪组织。因瘦素在脂肪组织制造，所以全身脂肪代谢障碍患者的瘦素水平很低。瘦素调节进食及其它激素，如胰岛素。

患有两种形式全身脂肪代谢障碍的患者常常在很小年龄时出现严重的胰岛素抵抗，可能会有难以控制的糖尿病，或血液中含有能导致胰腺炎的高水平甘油三酯。“Myalept是首个获批用于治疗先天性或获得性全身脂肪代谢障碍有关综合症的治疗药物，它可以为患有这种孤儿病的患者提供一种需要的治疗选择，”FDA药物评价与研究中心药物评价II办公室副主任、医学博士Mary Parks说。

Myalept是通过基因重组技术制成的一种模拟瘦素，它的安全性和有效性通过一项开放式标签的单一试验研究获得评价，有48名先天性或获得性全身脂肪代谢障碍，同时患有糖尿病、高甘油三酯血症和/或高水平空腹胰岛素的患者参与了该项研究。试验显示患者糖化血红蛋白（一种血糖控制指标）、空腹血糖和甘油三酯均有降低。

对瘦素和/或Myalept有中和活性的抗药抗体可能会出现，可导致严重感染或治疗效果丧失。使用或未使用Myalept治疗的获得性全身脂肪代谢障碍患者中已有T细胞淋巴瘤报道，

所以卫生保健专业人员在使用Myalept治疗有明显血液学异常和/或获得性全身脂肪代谢障碍患者时应该认真考虑治疗的收益和风险。

Myalept被禁用于普通肥胖患者。Myalept未被批准在患有HIV相关脂肪代谢障碍患者或患有代谢性疾病（包括糖尿病和高甘油三酯血症、无并发证据的全身脂肪代谢障碍）的患者身上使用。

由于存在发生中和抗体和淋巴瘤的风险，所以Myalept只能通过Myalept风险评估及降低策略(REMS)计划获得。根据REMS计划，开药者必须参加并完成培训以获得认证。

药房必须获得该计划的认证，并在收到用于每个新处方的Myalept REMS处方授权书之后才能分发Myalept。Myalept获批时也带有一份用药指南和说明，以提供患者有关这款药物的重要信息。该指南在患者每次申请处方时一并分发。

FDA要求对Myalept进行7项上市后研究，包括一项长期的Myalept用药患者前瞻性观察研究，一项评价Myalept免疫原性（抗体形成）的研究和一项有关Myalept使用潜在严重风险自发报告的评价和分析。8项其它研究被要求作为上市后的承诺。在临床试验中，Myalept治疗患者最常见的副作用有低血糖、头痛、体重减轻和腹痛。Myalept由位于圣地亚哥的Amylin制药上市销售。

FDA approves Myalept to treat rare metabolic disease

On Feb. 24, 2014, the U.S. Food and Drug Administration approved Myalept (metreleptin for injection) as replacement therapy to treat the complications of leptin deficiency, in addition to diet, in patients with congenital generalized or acquired generalized lipodystrophy.  

Generalized lipodystrophy is a condition associated with a lack of fat tissue. Patients with congenital generalized lipodystrophy are born with little or no fat tissue. Patients with acquired generalized lipodystrophy generally lose fat tissue over time. Because the hormone leptin is made by fat tissue, patients with generalized lipodystrophy have very low leptin levels. Leptin regulates food intake and other hormones, such as insulin.  

Patients with both types of generalized lipodystrophy often develop severe insulin resistance at a young age and may have diabetes mellitus that is difficult to control or very high levels of triglycerides in the blood (hypertriglyceridemia) that can lead to inflammation of the pancreas.

“Myalept is the first approved therapy indicated for treating the complications associated with congenital or acquired generalized lipodystrophy and provides a needed treatment option for patients with this orphan disease,” said Mary Parks, M.D., deputy director of the Office of Drug Evaluation II in the FDA’s Center for Drug Evaluation and Research.

The safety and effectiveness of Myalept, an analog of leptin made through recombinant DNA technology, were evaluated in an open-label, single-arm study that included 48 patients with congenital or acquired generalized lipodystrophy who also had diabetes mellitus, hypertriglyceridemia, and/or elevated levels of fasting insulin. The trial showed reductions in HbA1c (a measure of blood sugar control), fasting glucose, and triglycerides.  

Anti-drug antibodies with neutralizing activity to leptin and/or Myalept may develop, which could result in severe infections or loss of treatment effectiveness. T-cell lymphoma has been reported in patients with acquired generalized lipodystrophy, both treated and not treated with Myalept, so healthcare professionals should carefully consider the benefits and risks of treatment with Myalept in patients with significant hematologic abnormalities and/or acquired generalized lipodystrophy. Myalept is contraindicated in patients with general obesity. Myalept is not approved for use in patients with HIV-related lipodystrophy or in patients with metabolic disease, including diabetes mellitus and hypertriglyceridemia, without concurrent evidence of generalized lipodystrophy.

Because of the risks associated with the development of neutralizing antibodies and lymphoma, Myalept is available only through the Myalept Risk Evaluation and Mitigation Strategy (REMS) Program. Under this REMS program, prescribers must be certified with the program by enrolling in and completing training. Pharmacies must be certified with the program and only dispense Myalept after receipt of the Myalept REMS Prescription Authorization Form for each new prescription.

Myalept is also approved with a Medication Guide and instructions for use that provides patients with important information about the medication. The guide will be distributed each time a patient fills a prescription.

The FDA is requiring seven studies (post-marketing requirements) for Myalept, including a long-term prospective observational study (product exposure registry) of patients treated with Myalept, a study to assess for the immunogenicity (antibody formation) of Myalept, and an assessment and analysis of spontaneous reports of potential serious risks related to the use of Myalept. Eight additional studies are being requested as post-marketing commitments.

In clinical trials, the most common side effects observed in patients treated with Myalept were low blood sugar (hypoglycemia), headache, decreased weight, and abdominal pain.  

Myalept is marketed by San Diego-based Amylin Pharmaceuticals, L.L.C.

关键词： FDA Amylin Pharma 美曲普汀 瘦素缺乏症

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