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FDA Approves 2 New Diabetes Combos

IDegLira, LixiLan go head-to-head; FDA approves Novo Nordisk’s Xultophy and Sanofi’s Soliqua on the same day.

Both products, known as LixiLan and IDegLira during clinical trials, were delayed by 3 months at the  U.S. Food and Drug Administration (FDA) following recommendations for approval from FDA panels back in May. And yet the FDA has approved the two new competing combination products containing fixed doses of glucagonlike-peptide 1 (GLP-1) receptor agonists and long-acting insulins, from Sanofi and Novo Nordisk respectively, for the treatment of adults with type 2 diabetes.

Now the approval in the United States for the Sanofi product, LixiLan, is the first market worldwide for this combination of its GLP-1 receptor agonist lixisenatide (Lyxumia/Adlyxin) and insulin glargine (Lantus). It is indicated for the treatment of adults with type 2 diabetes inadequately controlled on basal insulin (less than 60 units a day) or lixisenatide.

From Sanofi To be known as Soliqua 100/33, the prefilled pen device contains a fixed dose of insulin glargine 100 U/mL and lixisenatide 33 µg/mL and is indicated for once-daily dosing covering 15 to 60 units of insulin glargine and 5 to 20 µg of lixisenatide.  The pen uses SoloStar technology, the most frequently used disposable insulin-injection platform.  Soliqua 100/33 will be available in retail pharmacies in the United States in January 2017.  In its Phase 3 program (n>1,900), Soliqua 100/33 demonstrated better HbA1c reduction vs. Lantus with the majority of patients (55% vs. 30%) achieving the American Diabetes Association (ADA) target of <7% at 30 weeks. Patients in the Soliqua 100/33 arm also had similar rates of documented (≤70mg/dL) hypoglycemia vs. patients in the Lantus arm.

Similarly, the Novo Nordisk product is a fixed-dose combination of 100/3.6 of insulin degludec (Tresiba) and the GLP-1 agonist liraglutide (Victoza). To be known as Xultophy, it is indicated once daily as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus inadequately controlled on basal insulin (less than 50 units daily) or liraglutide (less than or equal to 1.8 mg daily).

Xultophy 100/3.6 can be taken at the same time each day with or without food and will be available in a prefilled pen. It delivers doses from 10 to 50 units with each injection, and each unit of Xultophy 100/3.6 contains 1 unit of insulin degludec and 0.036 mg of liraglutide. The starting dose is 16 units (16-units insulin degludec and 0.58-mg liraglutide), and the maximum dose of 50 units corresponds to 50 units of insulin degludec and 1.8 mg of liraglutide.  Launch in the United States is anticipated in the first half of 2017, says Novo Nordisk.

The European Medicines Agency (EMA) has also just given the green light to Sanofi’s combination of insulin glargine and lixisenatide; it is likely to be formally approved in the European Union within a couple of months, where it will be known as Suliqua, with a slightly different choice of doses (insulin glargine 100 U/mL with lixisenatide 33 or 50 µg/mL).

The indication in the European Union also differs slightly — there Suliqua will be indicated in combination with metformin for the treatment of adults with type 2 diabetes mellitus to improve glycemic control when this has not been provided by metformin alone or metformin combined with another oral glucose-lowering medicinal product or with basal insulin.

The Novo Nordisk product, Xultophy, is already available in the European Union — similarly, it is indicated there to improve glycemic control in combination with oral glucose-lowering medicinal products when these alone or combined with basal insulin do not provide adequate glycemic control.

Both products combine a long acting insulin with a GLP-1 analogue – Xultopy brings together Tresiba and Victoza, while Soliqua (formerly known as LixiLan) combines Lantus with Adlyxin (Lxyumia outside the US). Both 2-in-1 once daily injectables aim to help patients not controlling their type 2 diabetes with insulin alone or with a GLP-1 alone.

There is little difference in the FDA approved labels of the drugs, and neither have on this occasion gained approval for patients who are new to injectable therapy.

Novo’s data from its phase 3b DUAL V trial, meanwhile, shows Xultophy treatment meant patients were up to 4.5 times more likely to achieve glycemic targets without hypoglycemia and weight gain compared to those taking Lantus.

This profile could give Xultophy an edge on its rival – it also has an advantage in limiting cases of hypoglycemia, as Sanofi’s combo could only match Lantus on this measure.  But Sanofi is likely to get its drug to market first – it says Soliqua will be available in pharmacies in the US from January, while Novo says Xultophy will reach the market ‘in the first half’ of 2017.

The recommendation for approval was based on data from clinical trials of IDegLira, including the DUAL™ phase 3 clinical trial program, which involved more than 3,000 adults with type 2 diabetes. In addition to the DUAL™ clinical trial program, both insulin degludec and liraglutide have been studied extensively in separate clinical trial programs and the products are commercially available across the globe.

In its Phase 3 program (n>1,900), Soliqua 100/33 demonstrated better HbA1c reduction vs. Lantus with the majority of patients (55% vs. 30%) achieving the American Diabetes Association (ADA) target of <7% at 30 weeks. Patients in the Soliqua 100/33 arm also had similar rates of documented (≤70mg/dL) hypoglycemia vs. patients in the Lantus arm.

Novo said Xultophy would be offered at a 20 percent discount to the combined price of Tresiba and Victoza, while Sanofi said Soliqua would cost about same as a GLP-1 drug.  Both new drugs are given as once-daily injections and are designed to improve glycemic control in adults with type 2 diabetes.

Practice Pearls:

  • First FDA approved combos containing a GLP-1 Inhibitor and a long acting insulin.
  • Both products will prevent the weight gain from the use of just insulin alone.
  • The approval came quickly due to the fact that each of the drugs had gone through prior clinical studies.

Diabetes Care 2016 Sep; dc161495. http://dx.doi.org/10.2337/dc16-149