Amylin Pharmaceuticals, Inc, Eli Lilly and Company and Alkermes, Inc announced that a meta-analysis of primary cardiovascular events across controlled clinical studies of three months or greater, from the Byetta (exenatide) injection database, showed no increased risk of cardiovascular events associated with exenatide use. This analysis was done in a manner consistent with US Food and Drug Administration's (FDA's) updated guidance for evaluating cardiovascular risk in type-2 diabetes agents.
Results of this analysis indicate that the relative risk of cardiovascular events in exenatide-treated patients, compared to controls, was 0.70 with a 95 per cent confidence interval of 0.38 - 1.31. In this analysis, cardiovascular events included cardiovascular mortality, myocardial infarction, stroke, hospitalization for acute coronary syndrome and revascularization procedures. This finding suggests there is no increased risk of exenatide on cardiovascular outcomes and will be used to support the cardiovascular safety of exenatide once weekly, a phase-3 investigational formulation of exenatide, the active ingredient in Byetta.
To determine if there are favourable cardiovascular effects of exenatide treatment, Lilly and Amylin intend to initiate a large cardiovascular outcomes trial with a superiority design that will evaluate the effects of exenatide once weekly on major cardiovascular events, compared to standard of care with traditional antidiabetes medications. The global study will be sponsored by Amylin and Lilly, and active 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, NC). The steering committee for this study is chaired by professor Rury Holman, FRCP, director, Diabetes Trial Unit, Oxford University, and Robert M Califf, 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."
"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, 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."
Byetta is the first and only FDA-approved incretin mimetic for the treatment of type 2 diabetes. Byetta exhibits many of the same effects as the human incretin hormone glucagon like peptide-1 (GLP-1). GLP-1 improves blood sugar after food intake through multiple effects that work in concert on the stomach, liver, pancreas and brain.
Amylin, Lilly, and Alkermes are working together to develop exenatide once weekly, a subcutaneous injection of exenatide for the treatment of type-2 diabetes based on Alkermes' proprietary technology for long-acting medications.