FDA专家组支持批准德谷胰岛素

马里兰州银泉——11月8日，美国食品药品管理局(FDA)顾问组基于17项临床试验数据，以8:4的投票结果，支持批准长效基础胰岛素类似物德谷胰岛素(IDeg)单独使用，或与速效胰岛素类似物门冬胰岛素的复方制剂(IDegAsp)联用，用于治疗1型和2型糖尿病。

但内分泌与代谢药物专家组成员在投票过程中，对临床试验数据Meta分析所显示出的心血管安全性问题迹象存在争议，这也是此次会议的主要议题。

专家组一致建议IDeg和IDegAsp生产商诺和诺德公司应开展心血管结局试验，以进一步调查有关安全性问题。在临床试验中，包括不稳定心绞痛、心血管死亡、卒中以及急性冠脉综合征的复合主要心血管事件(MACE)终点指标有所增加。虽然小组成员承认这可能出于偶然因素，但仍认为有必要进行调查。

FDA在批准药物的同时，有权要求生产商开展上市后安全性试验。

据诺和诺德公司介绍，为达到缓慢吸收的目的，IDeg注射后形成多六聚体，德谷胰岛素从可溶性储存库中缓慢、持续、长期释放，并具有平稳释药特点。该公司以商品名Novolog销售门冬胰岛素。

诺和诺德称，在纳入约6,500例1型或2型糖尿病成人患者的26周和52周Ⅲ期试验中，IDeg 或IDegAsp治疗患者与胰岛素对照药物治疗患者相比，基线血红蛋白水平A1c下降呈非劣效性，而餐后血糖水平更低，低血糖症(特别是夜间低血糖症)风险下降。

小组成员同意IDeg 和IDegAsp将有益于临床实践，包括与短效胰岛素复方制剂联用的有效性，以及作用时间可持续约24 h的证据。

一旦获批，该公司计划以预装胰岛素笔的形式推出德谷胰岛素及其复方产品，商品名分别为Tresiba和Ryzodeg。

虽然专家小组的推荐意见不具约束力，但FDA通常会采纳其建议。一般不允许与会议主题存在潜在利益冲突的小组成员参会，但此次会议有1名专家成员被豁免与会。

该公司已向欧洲、加拿大及其他国家提交了德谷胰岛素和德谷胰岛素/门冬胰岛素的批准申请。截止目前，该公司已于9月底获得日本批准。

爱思唯尔版权所有  未经授权请勿转载

By: ELIZABETH MECHCATIE, Clinical Endocrinology News Digital Network

SILVER SPRING, MD. – A Food and Drug Administration advisory panel voted 8-4 on Nov. 8 to support approval of insulin degludec (IDeg), a long-acting basal insulin analogue, used alone, and in a combined formulation with the fast-acting insulin analogue aspart (IDegAsp) for the treatment of type 1 and type 2 diabetes, based on clinical trial data from 17 studies.

But members of the Endocrinologic and Metabolic Drugs Advisory Committee struggled with their votes because of a cardiovascular safety signal detected in a meta-analysis of the clinical trials, the major issue discussed at the meeting.

The panel unanimously recommended that Novo Nordisk, the manufacturer of IDeg and IDegAsp, should conduct a cardiovascular outcomes trial to further investigate the safety signal, which was an increase in a composite major cardiovascular event (MACE) end point of unstable angina pectoris, cardiovascular death, stroke, and acute coronary syndrome. While panelists agreed the signal could be caused by chance, they also said that it should be investigated.

In approving a drug, the FDA has the authority to require that a company conduct a postmarketing safety trial.

Designed for slower absorption, IDeg forms multihexamers after injection, resulting in a soluble depot from which there is a slow, continuous, and extended release of insulin degludec, and a flat stable profile, according to Novo Nordisk, which markets insulin aspart as Novolog.

In phase III, 26- and 52-week studies of almost 6,500 adult patients with type 1 or type 2 diabetes, treatment with IDeg or IDegAsp was noninferior to insulin comparators in reducing hemoglobin A1c from baseline, and resulted in lower fasting blood glucose levels, with a reduced risk of hypoglycemia, particularly nocturnal hypoglycemia, according to Novo Nordisk.

Panelists agreed IDeg and IDegAsp had features that would be useful in clinical practice, including the availability in combination with a short-acting insulin and evidence that it lasts for about 24 hours.

If approved, the company plans to make both insulin degludec and the combination product available in prefilled insulin pens, and they will market the products as Tresiba and Ryzodeg.

The FDA usually follows the recommendations of its advisory panels, which are not binding. Panelists have been cleared of potential conflicts of interest related to the topic of the meeting, although a one panelist at this meeting was given a waiver.

The company has also submitted an application for approval of insulin degludec and insulin degludec/insulin aspart in Europe, in Canada, and other countries. To date, it has been approved in Japan, in late September.