Amylin Pharmaceuticals Inc., Eli Lilly and Company and Alkermes Inc. have submitted a New Drug Application (NDA) for exenatide once-weekly to the US Food and Drug Administration (FDA).
Exenatide once-weekly is an investigational sustained release medication for type 2 diabetes, which is injected subcutaneously and administered only once a week. Exenatide is the active ingredient in Byetta (exenatide) injection, which is currently available in the US and in many countries worldwide for people with type 2 diabetes who are unable to achieve good glycemic control with common oral therapies.
"The exenatide once weekly submission is an important milestone in the overall exenatide development programme. The clinical data supporting this submission highlight the potential of exenatide once weekly to significantly advance the treatment of type 2 diabetes," said Daniel M. Bradbury, president and chief executive officer of Amylin. "We remain committed to developing and commercializing a range of treatment options that address the important unmet needs of people living with diabetes."
Clinical components of the NDA include the DURATION-1 study and the meta-analysis of primary cardiovascular events across the Byetta clinical database. DURATION-1 was designed to test the superiority of exenatide once weekly, as compared to Byetta, which is administered twice daily. In this study, exenatide once weekly treatment resulted in statistically significant reductions in A1C of 1.9 percentage points from baseline, compared to a reduction of 1.5 percentage points for Byetta, and 77 percent of patients treated with exenatide once weekly achieved an A1C of 7 percent or less compared to 61 percent of patients treated with Byetta.
Exenatide once weekly and Byetta were both associated with an average weight loss of 8 pounds from baseline. The most commonly reported adverse event was nausea, which was typically mild and transient and occurred less frequently in the exenatide once weekly patients. In addition, a meta-analysis across controlled clinical studies of three months or greater from the Byetta database showed no increased risk of cardiovascular events associated with exenatide use. This analysis applied principles outlined in the FDA's guidance for evaluating cardiovascular risk in type 2 diabetes agents.
Components of the submission supporting product manufacturing include analyses to demonstrate comparability of the intended commercial product with that used during development. These analyses include data from patients in the ongoing extension of the DURATION-1 study who used exenatide once weekly produced at Amylin's manufacturing facility in Ohio.
"If approved, exenatide once weekly would be the first and only once-a-week therapy for the treatment of type 2 diabetes," said David Vondle, exenatide global brand development leader for Lilly. "A new treatment option to help patients with type 2 diabetes manage blood sugar, with potential weight loss and less frequent dosing, could offer an important advance in the treatment paradigm for patients and physicians who manage this chronic condition."
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. Byetta is approved by the FDA for use by people with type 2 diabetes who are unsuccessful at controlling their blood sugar levels. Byetta is an add-on therapy for people currently using metformin, a sulfonylurea, or a thiazolidinedione. Byetta provides sustained A1C control and low incidence of hypoglycemia when used with metformin or a thiazolidinedione, with potential weight loss. Byetta is not a weight loss product. Byetta was approved in April 2005 and has been used by more than one million patients since its introduction.
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. Exenatide once weekly is not currently approved by any regulatory agencies.
Amylin Pharmaceuticals is a biopharmaceutical company committed to improving lives through the discovery, development and commercialization of innovative medicines.
Lilly, a leading innovation-driven corporation, is developing a growing portfolio of first-in-class and best-in-class pharmaceutical products by applying the latest research from its own worldwide laboratories and from collaborations with eminent scientific organizations.
Alkermes, Inc. is a fully integrated biotechnology company committed to developing innovative medicines to improve patients' lives. Alkermes' robust pipeline includes extended-release injectable, pulmonary and oral products for the treatment of prevalent, chronic diseases, such as central nervous system disorders, addiction and diabetes.