US approval of the combination of the GLP-1 receptor agonist lixisenatide (Adylxin, Sanofi) and insulin glargine (Lantus, Sanofi), which will be known as LixiLan (formerly iGlarLixi) has been delayed by 3 months, as the Food and Drug Administration (FDA) has asked for more information from Sanofi.
In a statement, the company says the US agency has requested more details about the pen delivery device as part of the new drug application (NDA) for the investigational once-daily fixed-ratio combination of basal insulin glargine 100 units/mL and lixisenatide for the treatment of adults with type 2 diabetes.
"The additional information, submitted at FDA's request, constitutes a major amendment to the NDA, resulting in an extension of the Prescription Drug User Fee Act [PDUFA] goal date by 3 months, to November 2016," the company notes in a press statement.
This move means that a competitor product from Novo Nordisk is likely to make it to the US market first.
That combination of the GLP-1 agonist liraglutide (Victoza, Novo Nordisk) and the long-acting insulin degludec (Tresiba, Novo Nordisk) is also awaiting approval in the United States, with a decision expected any day now. Known as IDegLira in clinical trials, it is already approved in Europe under the brand name Xultophy .
FDA Panel Members Were Concerned About LixiLan Delivery Device
Although the FDA's Endocrinologic and Metabolic Drugs Advisory Committee voted 12-2 on May 25 to recommend approval of LixiLan as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus, a number of the committee members had reservations at the time about the pen device used to deliver the medications.
Sanofi had been proposing to deliver LixiLan to patients via the SoloStar pen, a device that has been used for years for insulin glargine.
The company suggests two dosage pens: pen A would be used by insulin-naive patients and provides medications in a 2:1 ratio, with 10 to 40 units of insulin glargine and 5 to 20 µg of lixisenatide. Pen B provides medications in a 3:1 ratio, with 30 to 60 units of insulin glargine combined with 10 to 20 µg of lixisenatide.
The company reported few errors in the understanding and use of the pens by pharmacists, patients, and physicians in its studies, but the FDA said it found that having two pens increases the potential for mistakes. The pen design also means that some users could receive a lower or higher dose, said the agency.
Panelists were concerned about the notion that the pens would be labeled in "units," because the term did not refer to insulin units or units of lixisenatide.
"I feel very strongly you cannot use the proposed pen," Ellen W Seely, MD, director of clinical research in endocrinology, diabetes, and hypertension at Brigham and Women's Hospital in Boston, Massachusetts, told the May meeting.
"We're not objecting to the notion of this construct altogether, but there's a challenge here in terms of how to adequately label [the pen device]…color it, structure it, and educate the people who will be using this," added another panel member.
Novo Nordisk's IDegLira was also recommended for approval by the same FDA Endocrinologic and Metabolic Drugs Advisory Committee in a unanimous 16-0 vote in May.
Sanofi's GLP-1/Insulin Combo LixiLan Faces 3-Month Delay in US. Medscape. Aug 25, 2016.