SAN DIEGO, and INDIANAPOLIS, and CAMBRIDGE, Massachusetts, October 31 /PRNewswire/ --
- U.S. New Drug Application Filing Planned by the End of the First Half of-2009 -
Amylin Pharmaceuticals, Inc., (Nasdaq: AMLN), Eli Lilly and Company (NYSE: LLY) and Alkermes, Inc. (Nasdaq: ALKS) today announced positive results from a 30-week Phase 2/3 study of once-weekly exenatide long-acting release (LAR) injection compared with BYETTA(R) (exenatide) injection taken twice daily in patients with type 2 diabetes.
Once-weekly exenatide demonstrated a statistically significant improvement in glycaemic control between the two treatments as measured by hemoglobin A1c (HbA1c). HbA1c is a measure of glucose control over the previous 3 months. Once-weekly exenatide lowered HbA1c by approximately 1.9 percentage points from baseline, compared to a lowering of approximately 1.5 percentage points for BYETTA. Nearly half of all patients taking once-weekly exenatide achieved an HbA1c target of 6.5 percent or less. (The International Diabetes Federation recommends a target HbA1c of 6.5 percent or less.)
Exenatide LAR is an investigational once-weekly formulation of exenatide. Exenatide is the active ingredient in BYETTA and is currently available in many countries worldwide for the treatment of type 2 diabetes. Exenatide is approved in the US as add-on therapy for people currently using metformin, a sulfonylurea, or a thiazolidinedione.
The study enrolled patients not achieving adequate glucose control with either diet and exercise or with use of one or more oral glucose-lowering agents. Nearly 90 percent of subjects in both treatment arms completed the study. After 30 weeks of treatment, both once-weekly exenatide and exenatide treatment resulted in an average weight loss of approximately 3.6 kilograms (8.0 pounds). Both exenatide and once-weekly exenatide were generally well tolerated. The companies anticipate a regulatory submission to the U.S. Food and Drug Administration (FDA) by the end of the first half of 2009.
"Together with our collaboration partners Lilly and Alkermes, we are pleased that use of once-weekly exenatide met the primary endpoint with a greater reduction in HbA1c, the key measure of success in the management of type 2 diabetes, and was associated with weight loss in some patients," said Orville G. Kolterman, M.D., Senior Vice President Clinical and Regulatory Affairs, Amylin Pharmaceuticals. "These data build on the benefits of exenatide as an important treatment option and suggest that once-weekly administration of exenatide has the potential to help patients further improve their diabetes control."
No cases of major or severe hypoglycaemia were reported in either treatment arm regardless of background therapy. Minor hypoglycaemia was reported with once-weekly exenatide use and was limited to subjects using background sulphonylurea therapy. Once-weekly exenatide was associated with approximately 30 percent less nausea than exenatide. Approximately one out of five subjects receiving once-weekly exenatide reported treatment-related nausea during the 30-week study. In both groups, nausea was predominantly mild and decreased with time. The antibody profile of subjects treated in this study was consistent with the previously reported profiles of exenatide and once-weekly exenatide.
BYETTA -- the first and only FDA-approved incretin mimetic -- was approved in April 2005 and has been used by more than 700,000 patients since its introduction in the United States. Exenatide is indicated for use in people with type 2 diabetes who are unsuccessful at controlling their blood sugar levels using common oral diabetes medications.
Once-weekly exenatide uses a proprietary technology for long-acting medications developed by Alkermes. The technology encapsulates active medication into polymer-based microspheres that are injected into the body where they degrade slowly, gradually releasing the drug at a carefully controlled rate.
The 30-week, open-label, non-inferiority study included 295 subjects with type 2 diabetes who were not achieving adequate glucose control using diet and exercise with or without the use of one or more oral antidiabetic agents. Subjects were randomised to receive subcutaneous injections of either once-weekly exenatide 2.0 milligrams or exenatide taken twice daily [5 mcg twice daily for 4 weeks and 10 mcg twice daily for the remainder of the study]. All subjects who completed the randomised portion of the study are continuing in an open-ended study receiving once-weekly exenatide.
Full study results will be included in future scientific publications.
Diabetes affects an estimated 246 million adults worldwide and more than 48 million in Europe(1,2). Approximately 90 to 95 percent of those are affected by type 2 diabetes, a condition characterised by failure of the pancreatic beta-cell to adequately respond to the increased demands for insulin and obesity-related insulin resistance(3). In western countries, around 90 percent of type 2 diabetes cases are attributable to weight gain(4). Type 2 diabetes usually occurs in adults over the age of 40, but is increasingly common in younger people(2). In virtually every developed society, diabetes is ranked among the leading causes of blindness, renal failure and lower limb amputation, as well as death through its effects on cardiovascular disease (70-80 percent of people with diabetes die of cardiovascular disease)(5). The calculated estimates of the costs of diabetes care in Europe amount to 42.8 billion International Dollars per year(6).
Exenatide is the first approved incretin mimetic, a class of class of drugs for the treatment of type 2 diabetes. Exenatide exhibits many of the same effects as the human incretin hormone glucagon-like peptide-1 (GLP-1). GLP-1, secreted in response to food intake, has multiple effects on the intestine, liver, pancreas and brain that work in concert to regulate blood sugar(7).
About Incretin Mimetics
Incretin mimetics are a distinct class of agents used to treat type 2 diabetes. An incretin mimetic works to mimic the anti-diabetic or glucose-lowering actions of the naturally occurring human incretin hormone GLP-1. 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 promoting satiety.
About BYETTA(R) (exenatide) injection
Exenatide is the first in a class of drugs for the treatment of type 2 diabetes called incretin mimetics. Exenatide 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. Exenatide is approved in the European Union as adjunctive therapy to improve blood sugar control in patients with type 2 diabetes who have not achieved adequate glycaemic control on maximally tolerated doses of metformin and/or a sulphonylurea, two common oral diabetes medications.
About Amylin, Lilly, and Alkermes
Amylin, Lilly, and Alkermes are working together to develop exenatide long-acting release injection, a subcutaneous injection of exenatide for the treatment of type 2 diabetes based on Alkermes' proprietary injectable long-acting release technology. Once-weekly exenatide has not been approved by the FDA for marketing in the United States or by regulatory agencies elsewhere in the world.
Amylin Pharmaceuticals is a biopharmaceutical company committed to improving lives through the discovery, development and commercialization of innovative medicines. Amylin has developed and gained approval for two first-in-class medicines for diabetes. Amylin's research and development activities leverage the company's expertise in metabolism to develop potential therapies to treat diabetes and obesity. Amylin is headquartered in San Diego, California with over 1,800 employees nationwide.
Through a long-standing commitment to diabetes care, Lilly provides patients with breakthrough treatments that enable them to live longer, healthier and fuller lives. Since 1923, Lilly has been the industry leader in pioneering therapies to help health care professionals improve the lives of people with diabetes, and research continues on innovative medicines to address the unmet needs of patients.
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. Headquartered in Indianapolis, Indiana, Lilly provides answers -- through medicines and information -- for some of the world's most urgent medical needs.
Alkermes, Inc. is a biotechnology company that develops innovative medicines designed to yield better therapeutic outcomes and improve the lives of patients with serious disease. Alkermes currently has two commercial products: the first and only long-acting atypical antipsychotic medication approved for use in schizophrenia which is marketed worldwide by Janssen-Cilag (Janssen), a wholly owned division of Johnson & Johnson; and the first and only once-monthly injectable medication approved for the treatment of alcohol dependence which is marketed in the U.S. primarily by Cephalon, Inc. Alkermes' pipeline includes extended-release injectable, pulmonary and oral products for the treatment of prevalent, chronic diseases such as diabetes, addiction and central nervous system disorders. Alkermes' headquarters are in Cambridge, Massachusetts, and it operates research and manufacturing facilities in Massachusetts and Ohio.
This press release contains forward-looking statements, which involve risks and uncertainties within the meaning of the Private Securities Litigation Reform Act of 1995. The forward-looking statements are neither promises nor guarantees, and the businesses of Amylin, Lilly and Alkermes are subject to significant risks and uncertainties. There can be no assurance that actual results will not differ materially from the forward-looking statements discussed in this press release. These forward-looking statements include risks and uncertainties, including but not limited to, that current or future clinical trials will confirm previous results; risks and uncertainties that the results from the clinical trial discussed in this press release will generate clinical data that could form the basis of an NDA submission; risks and uncertainties that Amylin will be able to complete manufacturing scale-up and construction and validation of its manufacturing facility on a timely basis, or at all; risks and uncertainties regarding the timing of the new drug application filing referred to in this release; risks and uncertainties inherent in the collaboration with and dependence upon Lilly, Amylin and/or Alkermes; risks and uncertainties regarding the drug discovery and development process, including whether exenatide LAR will receive regulatory approvals, be commercialized or prove to be commercially successful. These and additional risks and uncertainties are described more fully in Amylin, Lilly and Alkermes' filings with the United States Securities and Exchange Commission. The parties undertake no duty to update forward-looking statements.
(1) The International Diabetes Federation Diabetes Atlas. Available at: http://www.idf.org/home/index.cfm?unode=3B96906B-C026-2FD3-87B73F80BC2268 2A . Accessed June 14, 2007.
(2) The International Diabetes Federation, Prevalence / All diabetes. Available at http://www.eatlas.idf.org/Prevalence/All_diabetes/. Accessed October 29, 2007.
(3) Turner RC, Cull CA, Frighi V, Holman RR. Glycemic control with diet, sulfonylurea, metformin, or insulin in patients with type 2 diabetes mellitus: progressive requirement for multiple therapies (UKPDS 49). JAMA. 1999; 281 (21):2005-2012.
(4) The International Diabetes Federation Diabetes Atlas. Available at: http://www.eatlas.idf.org/Obesity_and_type_2_diabetes/ Accessed on October 29, 2007.
(5) The International Diabetes Federation, Complications. Available at http://www.eatlas.idf.org/Complications/ Accessed October 29, 2007.
(6) The International Diabetes Federation, Diabetes Atlas, Second edition. The Economic Impact of Diabetes. 2003: 186.
(7) Kolterman, O, Buse J, Fineman M, Gaines E, Heintz S, Bicsak T, Taylor K, Kim D, Aisporna M, Wang Y, Baron A. Synthetic exendin-4 (exenatide) significantly reduces postprandial and fasting glucose in subjects with type 2 diabetes. Journal of Clinical Endocrinology & Metabolism. 2003; 88(7):3082-3089.
Media contacts: - Alice Bahner Izzo of Amylin, +1-858-642-7272, or cell, +1-858-232-9072; Derin Denham of Lilly, +1-317-277-6749, or cell, +1-317-370-1435; Rebecca Peterson of Alkermes, +1-617-583-6378, or cell, +1-617-899-2447. Photo: http://www.newscom.com/cgi-bin/prnh/20040122/LILLYAMYLINLOGO , http://www.newscom.com/cgi-bin/prnh/20071031/CLW032LOGO , PRN Photo Desk, email@example.com