SAN FRANCISCO, June 10 /PRNewswire/ --
- Phase 3 Once Weekly Investigational Diabetes Therapy Also Improved Glucose Control in Patients Switching from Exenatide Taken Twice a Day -
Amylin Pharmaceuticals, Inc. (Nasdaq: AMLN), Eli Lilly and Company (NYSE: LLY), and Alkermes, Inc. (Nasdaq: ALKS) today announced results from a 52-week open label clinical study that showed the durable efficacy of exenatide once weekly, a long-acting release formulation of exenatide. Patients taking exenatide once weekly over the course of one year sustained a similar improvement in glucose control [HbA1c: -2.0%+/-0.08; fasting plasma glucose (FPG) -2.61+/-0.17 mmol/L] compared to those receiving treatment for 30 weeks [HbA1c change from baseline: 1.9%+/-0.08 (LS mean+/-SE)]. This study also showed that patients who switched from BYETTA(R) (exenatide) twice daily injection after 30 weeks to exenatide once weekly experienced additional improvements in HbA1c and fasting plasma glucose. Seventy-four percent of all patients in the study achieved an endpoint HbA1c of 7 percent or less at 52 weeks. Patients in both treatment groups experienced a statistically significant and sustained average weight loss of 4.3 kilograms over 52 weeks. These findings were presented at the 68th Annual Scientific Sessions of the American Diabetes Association (ADA) in San Francisco.
Exenatide once weekly is an investigational 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 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.
"Diabetes is a lifelong condition that requires constant management of blood glucose or blood sugar as well as weight. In the DURATION-1 trial, patients significantly reduced their blood glucose levels and, on average, lost a total of over four kilograms. These improvements were sustained for a year," said John B. Buse, M.D., Ph.D., Professor of Medicine, Director of the Diabetes Care Center, and Chief of the Division of Endocrinology at the University of North Carolina School of Medicine in Chapel Hill. "Importantly, the study results also showed that steady-state levels of exenatide may result in improvements in a variety of glucose parameters. If approved, exenatide once weekly may provide patients with a treatment option that is on board 24 hours a day, seven days a week, helping to manage their blood sugar and, secondarily, their weight."
The Diabetes Therapy Utilization: Researching Changes in A1C, Weight and Other Factors Through Intervention with Exenatide ONce Weekly (DURATION-1) study was a 30-week, randomized, open-label study of 295 patients with type 2 diabetes (baseline values: HbA1c 8.3%+/-1.0, FPG 9.38+/-2.38 mmol/L, weight 102+/-20 kg, BMI 35+/-5.0 kg/m2, diabetes duration 6.7+/-5.0 years; mean+/-SD) who were treated with exenatide once weekly 2.0 milligrams or exenatide twice daily as outlined in the approved label subcutaneously. Following the first 30 weeks of treatment, 258 patients entered an open-label treatment with exenatide once weekly. Patients either remained on exenatide once weekly or switched from exenatide to exenatide once weekly for an additional 22 weeks.
Following the 30-week comparison period, patients (evaluable population N=241) who continued on exenatide once weekly showed sustained improvements in HbA1c and fasting plasma glucose levels at week 52 [HbA1c: -2.0%+/-0.1; FPG -2.61+/-0.17 mmol/L (LS mean+/-SE)]. Patients who switched from exenatide to exenatide once weekly had further improvements in glycaemic control [HbA1c: -2.0%+/-0.1; FPG -2.39+/-0.17 mmol/L] that were consistent with those of patients receiving exenatide once weekly for 52 weeks. These data suggested the additional impact of continuous exenatide levels on glycaemic control.
In both groups, HbA1c reduction was similar at 52 weeks. Seventy-two percent of patients treated with exenatide once weekly achieved an endpoint HbA1c of 7 percent or less, and 54 percent achieved an HbA1c of 6.5 percent or less. In patients who switched from exenatide to exenatide once weekly, 75 percent of patients achieved an endpoint HbA1c of 7 percent or less, and 53 percent achieved an HbA1c of 6.5 percent or less. The International Diabetes Federation (IDF) recommends a target HbA1c of below 6.5 percent. Unlike the weight gain that is commonly associated with insulin therapy and many oral diabetes medications, exenatide once weekly was associated with an average body weight loss of 4.3 kilograms over 52 weeks.
Exenatide once weekly 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 in a controlled manner to provide continuous therapeutic exenatide levels in plasma.
Exenatide once weekly was well tolerated during the first 30 weeks of treatment and the following 22-week open-ended treatment period with overall tolerability improving over the course of the study. No major hypoglycaemia events, regardless of background therapy, were observed with exenatide once weekly. Cases of minor hypoglycaemia with exenatide once weekly and with exenatide use were limited to patients using background sulphonylurea therapy. In both groups, nausea was predominantly mild and transient and occurred less frequently in the exenatide once weekly patients. Patients switching from exenatide to exenatide once weekly did not experience significant increase in nausea following the transition. The antibody profiles of patients treated in this study were consistent with the previously reported profiles of exenatide and exenatide once weekly.
About BYETTA(R) (exenatide) Injection
Exenatide is the first and only approved incretin mimetic, a 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.(1) 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. Since the U.S. market introduction in June 2005, approximately one million patients worldwide have been treated with exenatide.
Diabetes affects an estimated 246 million adults worldwide and more than 48 million in Europe.(2,3) Approximately 90 to 95 percent of those are affected by type 2 diabetes, a condition characterized by failure of the pancreatic beta-cell to adequately respond to the increased demands for insulin that occur as a result of obesity-related insulin resistance.(4) In western countries, around 90 percent of type 2 diabetes cases are attributable to weight gain.(5)
Type 2 diabetes usually occurs in adults over the age of 40, but is increasingly common in younger people.(6) 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).(7) The calculated estimates of the costs of diabetes care in Europe amount to 42.8 billion International Dollars per year.(8)
Important Safety Information for exenatide
In clinical studies, the most common side effects were hypoglycaemia (low blood sugar) when taken with a sulphonylurea, nausea (feeling sick), vomiting and diarrhea. For the full list of all side effects reported with exenatide, see the Package Leaflet. Exenatide should not be used in people who may be hypersensitive (allergic) to exenatide or any of the other ingredients.
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 reducing food intake.
About Amylin, Lilly and Alkermes
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. 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 2,000 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 healthcare 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 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. Headquartered in Cambridge, Massachusetts, Alkermes has research and manufacturing facilities in Massachusetts and Ohio.
This press release contains forward-looking statements about Amylin, Lilly and Alkermes. Actual results could differ materially from those discussed or implied in this press release due to a number of risks and uncertainties, including the risk that exenatide and the revenues generated from exenatide may be affected by competition; unexpected new data; technical issues; clinical trials not confirming previous results; pre-clinical trials not predicting future results; new drug applications and label expansion requests, not being submitted in a timely manner or receiving regulatory approval; or manufacturing and supply issues. The potential for exenatide may also be affected by government and commercial reimbursement and pricing decisions, the pace of market acceptance, or scientific, regulatory and other issues and risks inherent in the commercialization of pharmaceutical products. These and additional risks and uncertainties are described more fully in the companies' most recently filed United States Securities and Exchange Commission documents including their Quarterly Reports on Form 10-Q and Annual Reports on Form 10-K. The companies undertake no duty to update these forward-looking statements.
(1) 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.
(2) The International Diabetes Federation Diabetes Atlas. Available at: http://www.idf.org/home/index.cfm?unode=3B96906B-C026-2FD3-87B73F80BC22682A. Accessed on May 22, 2008.
(3) The International Diabetes Federation, Prevalence / All diabetes. Available at: http://www.eatlas.idf.org/Prevalence/All_diabetes/. Accessed on May 22, 2008.
(4) 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.
(5) The International Diabetes Federation Diabetes Atlas. Available at: http://www.eatlas.idf.org/Obesity_and_type_2_diabetes/. Accessed on May 22, 2008.
(6) The International Diabetes Federation, Prevalence / All diabetes. Available at http://www.eatlas.idf.org/Prevalence/All_diabetes/. Accessed on May 22, 2008.
(7) The International Diabetes Federation, Complications. Available at http://www.eatlas.idf.org/Complications/. Accessed on May 22, 2008.
(8) The International Diabetes Federation, Diabetes Atlas, Second edition. The Economic Impact of Diabetes. 2003: 186.
Lilly: Derin Denham, +1-317-277-6749 office, or +1-317-370-1435 mobile; or Amylin: Alice Izzo, +1-858-642-7272 office, or +1-858-232-9072 cell; or Alkermes: Rebecca Peterson, +1-617-583-6378 office, or +1-617-899-2447 cell. Photo: http://www.newscom.com/cgi-bin/prnh/20031219/LLYLOGO ; http://www.newscom.com/cgi-bin/prnh/20071031/CLW032LOGO ; http://www.newscom.com/cgi-bin/prnh/20060610/AMYLINLOGO ; AP Archive: http://photoarchive.ap.org ; PRN Photo Desk, firstname.lastname@example.org