AZ’s Bydureon disappoints in diabetes outcomes trial

AstraZeneca has had a setback to its ambitions in diabetes, after Bydureon failed to show cardiovascular benefits to patients.

The FDA now obliges companies with diabetes products to conduct large scale cardiovascular outcomes trials, and the once weekly GLP-1 drug Bydureon was studied for its effects on a composite measure of major adverse CV events (MACE).

The Phase 3b/4 EXSCEL (EXenatide Study of Cardiovascular Event Lowering) showed the drug did not increase cardiovascular (CV) risk, but an observed reduction in cases of heart attacks and strokes failed to reach statistical significance.

This is in contrast to Lilly and Boehringer's oral SGLT2 drug Jardiance, which now has the upper hand in the market, as it is the first drug able to claim cardiovascular benefits to diabetes patients.

Novo Nordisk's rival GLP-1 treatment Victoza is close behind, and is expected to gain FDA approval for similar claims this year, with a next generation GLP-1 drug semaglutide also awaiting approval.

The Phase 3b/4 EXSCEL (EXenatide Study of Cardiovascular Event Lowering) trial enrolled more than 14,000 type 2 diabetes patients, making it one of the biggest of its kind.

The trial compared the effect of once-weekly Bydureon (exenatide extended-release) versus placebo, when added to usual type-2 diabetes care, on the risk of MACE, a composite endpoint of CV death, non-fatal myocardial infarction or non-fatal stroke, in adults with type-2 diabetes (T2D) at a wide range of CV risk.

The news is a blow for AZ and its cardiovascular and metabolic business unit, which is one of its main growth platforms.

However the company does have a SGLT2 drug, Farxiga, which could have a similar CV profile to Jardiance.

In March, AstraZeneca announced an analysis of real world data from more than 300,000 patients across six countries taking SGLT2 drugs, including Farxiga, Jardiance and Janssen's Invokana.

The study found the drugs lowered the rate of hospitalisation for heart failure by 39% and death from any cause by 51% compared to other type 2 diabetes medicines.

However as Jardiance is currently the only drug in the class cleared to make CV claims, this study might boost Lilly and Boehringer's drug more than the class as a whole.

A wealth of new data will be presented by these and other companies in this increasingly competitive field at the American Diabetes Association annual meeting, which opens on 9 June.