GLP-1 Agonist Lixisenatide (Adlyxin) Okayed for Type 2 Diabetes in US


July 28, 2016

The US Food and Drug Administration (FDA) has approved the once daily subcutaneously injected glucagonlike-receptor (GLP-1) agonist lixisenatide (Adlyxin, Sanofi) for the treatment of adults with type 2 diabetes, as an adjunct to diet and exercise, the company has announced.

Lixisenatide is already approved in more than 60 countries worldwide and marketed in over 40, under a different brand name of Lyxumia; these include most countries of the European Union, Japan, Brazil, Mexico, and India.

First approvals for the agent came in 2013, but Sanofi withdrew its application with the US FDA for lixisenatide in that same year, stating that it wanted to wait for the results of the Evaluation of Lixisenatide in Acute Coronary Syndrome (ELIXA) trial, a cardiovascular-safety study of lixisenatide. CV safety studies of all newer drugs for the treatment of type 2 diabetes were mandated by the FDA in 2008.

The ELIXA trial was first reported last year, at the ADA meeting, and later published in the New England Journal of Medicine, showing that in patients with type 2 diabetes who had a recent acute coronary syndrome, lixisenatide did not lead to any increased cardiovascular adverse events compared with placebo — the results were totally neutral in every aspect.

The aim of these FDA-mandated CV outcomes trials has always been to demonstrate safety (ie, absence of harm) and not benefit.

However, two such trials have more recently and unexpectedly shown evidence of cardiovascular benefit with type 2 diabetes drugs, one of these being with another GLP-1 agonist, liraglutide (Victoza, Novo Nordisk), in the LEADER trial, reported at last month's ADA meeting.

Thus, lixisenatide will enter a difficult market in the United States, given that liraglutide has been on the market for some years there and has the advantage of the positive LEADER outcome trial rather than the neutral ELIXA findings.

Nevertheless, the US approval of lixisenatide also paves the way for approval of a combination product incorporating lixisenatide with Sanofi's insulin glargine (Lantus), known as iGlarLixi.

That product combines fixed doses of insulin glargine with lixisenatide in a pen device and was recommended for approval by an FDA advisory committee in May. The panel voted 12 to 2 to approve the product, although some had reservations about the pen device employed to deliver the combination and allergic reactions.

Sanofi notes that the approval of lixisenatide in the US is based on FDA review of results from the GetGoal clinical programs, as well as the findings from the ELIXA trial, "which successfully addressed the FDA's request to demonstrate CV safety."

The GetGoal clinical program included 13 clinical trials involving more than 5000 adults with type 2 diabetes worldwide and evaluated the safety and efficacy of lixisenatide. All studies in this program successfully met the primary efficacy end point of HbA1c reduction. The most common adverse events reported for lixisenatide included nausea, hypoglycemia, and vomiting.

Lixisenatide will be available in the United States as Adlyxin in a disposable prefilled pen in a single dose of 20 µg. Patients will also receive a disposable prefilled pen in a single dose of 10 µg that they should initiate once daily for 14 days. On day 15, patients will increase dosage to 20 µg once daily.

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