FDA批准GLP-1受体激动剂阿必鲁泰用于2型糖尿病治疗

美国食品药品管理局（FDA）已批准每周1次皮下注射剂阿必鲁泰（albiglutide）结合饮食和锻炼，用于改善2型糖尿病患者的血糖控制。

阿必鲁泰属于胰高血糖素样肽-1（GLP-1）受体激动剂，将由葛兰素史克（GSK）以商品名Tanzeum上市。FDA药品评价和研究中心药品评价2室主任Curtis Rosebraugh博士在声明中指出，该药物“可单独或与现有治疗方案联合应用，在对糖尿病患者整体管理中控制血糖水平。” 

该批准令是基于HARMONY项目结果。该项目包括8项临床试验，共计纳入2,000余例阿必鲁泰治疗患者。研究者比较了阿必鲁泰与2型糖尿病患者常用药物（包括胰岛素、二甲双胍、格列美脲和吡格列酮）对不同疾病阶段患者和肾脏损伤患者的有效性和安全性。

结果显示，阿必鲁泰治疗患者糖化血红蛋白A1c （HbA1c）水平得到改善。不过，最近发表的HARMONY 7试验结果显示，阿必鲁泰降低HbA1c水平不及另一GLP-1受体激动剂——每日1次的利拉鲁肽（Lancet Diabetes Endocrinol. 2014;2:289-97）。

阿必鲁泰是美国上市的第3个GLP-1受体激动剂。艾塞那肽（Byetta）于2005年获准上市，扩大适应症申请于2009年获批，用作改善2型糖尿病患者血糖控制的单药治疗。利拉鲁肽（Victoza）于2010年获准上市。这类生物制品能够促进葡萄糖依赖的胰岛素分泌，并延缓胃排空。

阿必鲁泰每周给药1次， 皮下注射，使用5-mm、29号薄管针头注射笔。上市规格有30 mg 和50 mg两种。需要进一步血糖控制的患者，每周用药剂量可增至50 mg。

阿必鲁泰未被推荐为一线治疗用药，也不应该用于1型 糖尿病患者或糖尿病酮酸中毒的治疗。尚未进行该药物在严重胃肠道疾病患者中的研究或与餐时胰岛素合用的研究。

该药物附带了一项潜在甲状腺C细胞腺瘤的黑框警告，因为某些GLP-1受体激动剂在啮齿类动物研究中观察到甲状腺C细胞腺瘤。FDA称，阿必鲁泰不应用于甲状腺髓样瘤个人或家族史患者或2型多发性内分泌肿瘤综合征患者。GSK还建议胰腺炎史患者应考虑使用其他替代治疗药物，一旦患者疑似胰腺炎，应立即停用阿必鲁泰。

试验中最常见不良反应为上呼吸道感染、腹泻、恶心和注射部位反应。

FDA要求GSK开展数项上市后研究：一项是评价儿童患者的剂量、有效性和安全性，另一项是评价心血管疾病基线高风险患者的心血管风险。GSK还将建立一项至少为持续15年的髓样甲状腺瘤登记库，以确认是否存在与阿必鲁泰相关的髓样甲状腺瘤发生率增加。

该批准令还附带了风险评估与减轻策略（REMS），包括制定一项告知医疗人员有关与该药物相关严重风险的沟通计划。

GSK预计阿必鲁泰将在秋季上市。该药物已于3月获准在欧洲上市，商品名为Eperzan。

爱思唯尔版权所有  未经授权请勿转载

By: ALICIA AULT, Clinical Endocrinology News Digital Network

Albiglutide, a once-weekly subcutaneous injection, has been approved by the Food and Drug Administration to improve glycemic control, in conjunction with diet and exercise in type 2 diabetes.

Albiglutide, which will be marketed as Tanzeum by GlaxoSmithKline, "can be used alone or added to existing treatment regimens to control blood sugar levels in the overall management of diabetes," said Dr. Curtis Rosebraugh, director of the Office of Drug Evaluation II in the FDA Center for Drug Evaluation and Research, in a statement.

The FDA approval is based on the results of the HARMONY program, which had eight trials involving more than 2,000 patients who received albiglutide. The glucagon-like peptide-1 (GLP-1) receptor agonist was compared with commonly used type 2 diabetes therapies, including insulin, metformin, glimepiride, and pioglitazone, in patients at different stages of the disease and in those with renal impairment.

Patients given albiglutide showed an improvement in their hemoglobin A1c levels. However, in HARMONY 7, published recently (Lancet Diabetes Endocrinol. 2014;2:289-97), albiglutide did not reduce HbA1c levels as much as another GLP-1 receptor agonist, once-daily liraglutide.

Albiglutide is the third GLP-1 receptor agonist to reach the U.S. market. Exenatide (Byetta), approved in 2005, gained an expanded indication in 2009, as monotherapy for improving glycemic control in type 2 diabetes. Liraglutide (Victoza) was approved in 2010. This class of biologic drugs promotes glucose-dependent insulin secretion and slows gastric emptying.

Administration of the drug is once weekly, subcutaneously, using an injector pen supplied with a 5-mm, 29-gauge thin-walled needle. It comes in two formulations, 30 mg and 50 mg. The dose can be increased to 50 mg once weekly in patients requiring additional glycemic control.

Albiglutide is not recommended as a first-line therapy and should not be used to treat type 1 diabetes or in patients with diabetic ketoacidosis. The drug has not been studied in patients with preexisting severe gastrointestinal disease or in combination with prandial insulin.

And the drug has a boxed warning on the potential for thyroid C-cell tumors, which have been observed in rodent studies with some GLP-1 receptor agonists. The FDA says that albiglutide should not be used in patients with a personal or family history of medullary thyroid carcinoma or in patients with multiple endocrine neoplasia syndrome type 2. GSK also suggests that alternatives be considered in patients with a history of pancreatitis, and that albiglutide should be discontinued immediately if pancreatitis is suspected.

The most frequent adverse reactions in trials were upper respiratory tract infection, diarrhea, nausea, and injection site reaction.

The FDA is requiring GSK to conduct several postmarketing studies: one to evaluate dosing, efficacy, and safety in pediatric patients, and another to evaluate cardiovascular risk in patients with high baseline risk of cardiovascular disease. GSK will also establish a medullary thyroid carcinoma registry that lasts at least 15 years to identify any increase in incidence that might be related to albiglutide.

The drug was approved with a Risk Evaluation and Mitigation Strategy (REMS), which consists of a communication plan to inform health care providers about the serious risks associated with it.

The company said it expects that albiglutide will be available in the fall. The drug – under the brand name Eperzan – received European approval in March.