A long-term comparator clinical study of a long-acting release (LAR) formulation of Byetta (exenatide) injection in patients with type 2 diabetes has been initiated following discussions with the US FDA. This study is designed to generate the type of safety and efficacy data that could form the basis of a New Drug Application (NDA), Amylin Pharmaceuticals, Inc., Eli Lilly and Company and Alkermes, Inc. announced here.

According to a company release, the 30-week open-label, non-inferiority study will assess whether once-weekly exenatide LAR is at least as effective in improving glucose control as twice-daily Byetta. Approximately 300 subjects with type 2 diabetes who are not achieving adequate glucose control using diet and exercise with or without the use of oral antidiabetic agents will be randomized to one of two treatment groups. Subjects randomized to the exenatide LAR group will receive once-weekly subcutaneous injections of a single strength of exenatide LAR. Subjects randomized to the comparison group will receive twice-daily injections of 10 micrograms of Byetta. Endpoints include change in haemoglobin A1C (a standard measure of glucose control), fasting blood glucose, body weight, and safety parameters. All participants who complete the randomized portion of the study will have the opportunity to continue in an extension study and receive once-weekly exenatide LAR.

In parallel with clinical activities, manufacturing process development and scale-up activities are underway. The material for this study is being manufactured at development scale, and the Companies are working to determine the overall manufacturing strategy. In December 2005, Amylin purchased a facility for the commercial production of exenatide LAR and expects to finalize the commercial manufacturing process for exenatide LAR by late 2008, stated the release.

Byetta was approved by the FDA in April 2005 for the treatment of type 2 diabetes as add-on therapy in patients who are not achieving acceptable blood sugar control despite using the commonly prescribed diabetes medications metformin, a sulfonylurea or a combination of both. Amylin, Lilly, and Alkermes are working together to develop a sustained release, subcutaneous injection of exenatide for the treatment of type 2 diabetes based on Alkermes' proprietary Medisorb technology. Exenatide LAR has not been approved by the FDA for marketing in the United States.

Incretin mimetics is a new class of therapeutic agents in the fight against diabetes. An incretin mimetic works to mimic the antidiabetic or glucose-lowering actions of naturally occurring human hormones called incretins. These actions include stimulating the body's ability to produce insulin in response to elevated levels of blood sugar, inhibiting the release of a hormone called glucagon following meals, slowing the rate at which nutrients are absorbed into the bloodstream and reducing food intake. Byetta is the first FDA-approved agent of this new class of medications.