Amylin Pharmaceuticals, Inc., Eli Lilly and Company and Alkermes, Inc. announced that their diabetes drug Byetta (exenatide) was not linked to increased cardiovascular events, strokes or other cardiovascular side effects.

The analysis was conducted in a manner consistent with U. S. Food and Drug Administration's (FDA's) updated guidance for evaluating cardiovascular risk in type 2 diabetes agents.

The data will be used to support the safety of Byetta in a once a week format while the current requirement is twice a day. The FDA asked for additional data on the new version of the drug in November.

Byetta, a synthetic hormone that stimulates cells in the pancreas to produce insulin when blood sugar is high, is marketed by Lilly, of Indianapolis, with San Diego-based Amylin. Alkermes Inc., of Cambridge, Massachusetts, is helping to develop the once-weekly treatment.

In December the FDA had requested that all proposed new treatments for Type 2 diabetes rule out an "unacceptable increase" in cardiovascular events before getting approved and Lilly and Amylin said the cardiovascular analysis "is consistent" with FDA's request. The companies plan to resubmit their application to the FDA by the end of the second quarter.

The companies said an analysis of the drug showed no increased risk of exenatide on cardiovascular outcomes which included cardiovascular mortality, myocardial infarction, stroke, hospitalization for acute coronary syndrome and revascularization procedures. This finding will be used to support the cardiovascular safety of exenatide once weekly, a phase 3 investigational formulation of exenatide, the active ingredient in BYETTA.

The analyses to demonstrate comparability necessary for the regulatory submission of exenatide once weekly have been successfully completed and will be part of the New Drug Application, NDA submitted to FDA.

These analyses include data from the ongoing extension of the DURATION-1 study, and will be used to support comparability between intermediate-scale clinical trial material made in Alkermes' manufacturing facility and commercial-scale drug product made at Amylin's manufacturing facility.

"Both the manufacturing comparability data and the meta-analysis of the exenatide clinical trial database are key components of our submission. We believe that the material made at commercial scale is comparable to the clinical-scale material, and we are confident that we will have a strong submission package for exenatide once weekly," said Orville G. Kolterman, M. D., senior vice president of research and development at Amylin. "If approved, this therapy has the potential to become the first weekly therapy to treat type 2 diabetes with glucose control and weight loss. This could offer a unique value proposition for patients, payers and physicians."

Lilly and Amylin intend to initiate a large cardiovascular outcomes trial to evaluate the effects of exenatide once weekly on major cardiovascular events, compared to standard of care with traditional anti-diabetes medications. The global study will be sponsored by Amylin and Lilly, and discussions are ongoing to have the study led by two academic research centers, The Diabetes Trial Unit at the Oxford Centre for Diabetes (Oxford, England) and Duke Clinical Research Institute at Duke University
(Durham, N. C.).

The steering committee for this study is chaired by Professor Rury Holman, FRCP, director, Diabetes Trial Unit, Oxford University, and Robert M. Califf, M. D., vice chancellor for clinical research and professor of medicine in the Division of Cardiology at Duke.

"There is a major unmet need for proven therapies that can help reduce the excess cardiovascular morbidity and mortality associated with type 2 diabetes," commented Professor Holman. "This trial is designed to determine the extent to which exenatide may reduce cardiovascular risk, in addition to lowering glucose."