ELIXA Completed; Diabetes Drug Lixisenatide Heads Back to FDA

Miriam E Tucker

March 19, 2015

Sanofi has released top-line results of its Evaluation of Lixisenatide in Acute Coronary Syndrome (ELIXA) study, the cardiovascular-outcomes trial for its glucagonlike peptide (GLP-1) agonist for the treatment of type 2 diabetes, lixisenatide (Lyxumia).

The results show that the cardiovascular-safety profile of lixisenatide is noninferior, although not superior, to placebo for cardiovascular safety, said the company, which will present the full data at the American Diabetes Association (ADA) Scientific Sessions in Boston on June 8.

Sanofi is also is planning to resubmit its US marketing application for lixisenatide later this year, following completion of ELIXA, which began in 2010 and involved 6000 patients with recent coronary events.

Lixisenatide, a once-daily injectable agent, has been on the market in Europe, Japan, Australia, and Mexico since 2013, but Sanofi withdrew its application with the US Food and Drug Administration (FDA) that same year because at the time the ELIXA study was not yet completed and the company decided against releasing interim data.

ELIXA was designed to satisfy the FDA's 2008 requirement for cardiovascular-safety studies for all new type 2 diabetes drugs, the results of which are now starting to trickle out.

If approved in the United States, lixisenatide would be the first GLP-1 receptor agonist with long-term cardiovascular-safety data in people living with diabetes who have very high CV risk, according to a company statement.

Another cardiovascular-safety study — LEADER — with liraglutide (Victoza, Novo Nordisk), the GLP-1 agonist that has been on the market for longestis being conducted in more than 8000 patients > 60 years with cardiovascular disease, peripheral arterial disease, chronic kidney disease, or other CV risk factors and is expected to complete later this year.

And there are ongoing CV safety trials with other GLP-1 agonists, including SUSTAIN 6 with semaglutide (Novo Nordisk), EXSCEL with exenatide (Byetta, AstraZeneca/Bristol-Myers Squibb) and REWIND with dulaglutide (Lilly).

Sanofi is also anticipating positive news this year on its once-daily fixed combination of lixisenatide and insulin glargine (Lantus).

Results from two phase 3 clinical studies — LIXILAN-O in insulin-naive type 2 diabetes patients and LIXILAN-L for those already on basal insulin — are expected later this year, according to the company statement.

More Cardiovascular-Outcomes Data With DPP-4 Inhibitor also at ADA

Also to be reported at the ADA meeting will be the cardiovascular-outcomes trial with another type of 2 diabetes drug, the dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin (Januvia, Merck).

The findings of that study, the Trial to Evaluate Cardiovascular Outcomes After Treatment With Sitagliptin (TECOS), are eagerly awaited because two other large outcomes trials with DPP-4 inhibitors, the Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus-TIMI 53 (SAVOR TIMI 53) with Onglyza (Bristol-Myers Squibb/AstraZeneca) and EXAMINE with alogliptin (Nesina, Takeda Pharmaceuticals), unearthed a possible increased risk for heart failure associated with the use of these agents in patients with type 2 diabetes.

The SAVOR-TIMI 53 results showed a significantly increased risk for hospitalization for heart failure in those taking saxagliptin vs those on placebo (hazard ratio [HR], 1.27; P = .007).

Although in EXAMINE there was a trend toward a higher risk for heart-failure hospitalization in patients taking alogliptin, new data from EXAMINE do not suggest an increased risk.

On April 14, both SAVOR TIMI 53 and EXAMINE will be discussed at a US FDA advisory committee meeting.

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