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。
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.