Type 2 Diabetes Patients Taking Exenatide Once Weekly, a Phase 3 Investigational Diabetes Therapy, Showed Improvements in Glycemic Control, Weight

DURATION-1 Data Presented at the 68th Annual Scientific Sessions of the American Diabetes Association

SAN FRANCISCO, June 07, 2008 /PRNewswire-FirstCall/ -- Amylin Pharmaceuticals, Inc. , Eli Lilly and Company , and Alkermes, Inc. announced results from a 30-week study that compared the efficacy of exenatide once weekly, a long-acting release formulation of exenatide, to BYETTA(R) (exenatide) injection. Type 2 diabetes patients treated with exenatide once weekly, an investigational therapy, showed statistically significant improvements in A1C (-1.9%+/-0.08 (LS mean+/-SE)) and fasting plasma glucose (FPG -42+/-3 mg/dL) from baseline and compared with BYETTA (-1.5%+/-0.08, A1C and -25+/-3 mg/dL, FPG). Patients in both treatment groups also reported significant weight loss (average of 8 pounds) and 77 percent of patients treated with exenatide once weekly achieved an A1C of 7 percent or less. These findings were presented at the 68th Annual Scientific Sessions of the American Diabetes Association (ADA) in San Francisco.

BYETTA is indicated as adjunctive therapy to improve glycemic control in patients with type 2 diabetes mellitus who are taking metformin, a sulfonylurea, a thiazolidinedione, a combination of metformin and a sulfonylurea, or a combination of metformin and a thiazolidinedione but have not achieved adequate glycemic control.

"We know that a substantial number of type 2 diabetes patients are overweight, and conventional diabetes therapies, while controlling blood glucose, may have little or no beneficial impact on body weight. Importantly, the DURATION-1 results suggested the significant, beneficial impact of continuous levels of exenatide once weekly on glycemic control, and additionally, weight loss," said Daniel J. Drucker, M.D., Professor in the Division of Endocrinology, Department of Medicine, of Toronto, Director of the Banting and Best Diabetes Centre.

Study Design and Findings

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: A1C 8.3%+/-1.0, FPG 169+/-43 mg/dL, weight 225+/-44 lbs., BMI 35+/-5.0 kg/m2, diabetes duration 6.7+/-5.0 years; mean+/-SD) who were treated with exenatide once weekly 2.0 mg or BYETTA twice daily as outlined in the approved label subcutaneously. Patients in both groups who completed the randomized portion of the study continued in an open-ended portion of the study to receive exenatide once weekly. Patients in both treatment arms showed improvements in A1C from baseline. In addition, treatment with exenatide once weekly resulted in statistically significant reductions in A1C [A1C change from baseline: 1.9%+/-0.08] compared to BYETTA [A1C change from baseline: 1.5%+/-0.08 (P=0.002)].

Seventy-seven percent of patients treated with exenatide once weekly achieved an A1C of 7 percent or less versus 61 percent for BYETTA (P=0.004). The ADA-recommended target for good glucose control is an A1C of below 7 percent. For patients entering the study with a baseline A1C of 9 percent or greater, at endpoint, 29 percent of patients treated with exenatide once weekly achieved A1C levels of 6.5 percent or less versus 13 percent for BYETTA. Both BYETTA and exenatide once weekly treatment groups showed significant glycemic improvements irrespective of baseline A1C.

Treatment with exenatide once weekly also resulted in significant lowering of FPG concentrations (reductions of -42+/-3 mg/dL, exenatide once weekly; - 25+/-3 mg/dL, BYETTA, P<0.0001 vs. BYETTA). Unlike the weight gain that is commonly associated with insulin therapy and many oral diabetes medications, both BYETTA and exenatide once weekly were associated with an average weight loss of 8 pounds.

In addition to weight loss, patients treated with exenatide once weekly experienced the following effects on several cardiovascular risk factors, including total cholesterol (total cholesterol -11.9+/-2.3 mg/dL from baseline 173 mg/dL; LDL -4.9+/-2.0 mg/dL from baseline 91.6 mg/dL; HDL -0.9+/-0.6 mg/dL from baseline 43.9 mg/dL) and triglycerides (15 percent improvement of mean ratio of week-30 to baseline from a baseline of 166.0 mg/dL).

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 concentrations.

Safety Profile

Exenatide once weekly was well tolerated with nearly 90 percent of patients completing 30 weeks of treatment. There were no major hypoglycemia events regardless of background therapy. Cases of minor hypoglycemia with exenatide once weekly and with BYETTA use were limited to patients using background sulfonylurea therapy. In both groups, nausea was predominantly mild and transient and occurred less frequently in the exenatide once weekly patients. Twenty-six percent of patients receiving exenatide once weekly reported nausea during the 30-week study. The antibody profiles of patients treated in this study were consistent with the previously reported profiles of BYETTA and exenatide once weekly. These data further supported the known safety profile of the exenatide molecule.

About BYETTA(R) (exenatide) injection

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, low incidence of hypoglycemia when used with metformin or a thiazoladinedione, and progressive weight loss. BYETTA was approved in April 2005 and has been used by approximately one million patients since its introduction.

About Diabetes

Diabetes affects more than 21 million in the United States and an estimated 246 million adults worldwide.(1,2) Approximately 90-95 percent of those affected have type 2 diabetes. Diabetes is the fifth leading cause of death by disease in the United States and costs approximately $132 billion per year in direct and indirect medical expenses.(3)

According to the Centers for Disease Control and Prevention's National Health and Nutrition Examination Survey, approximately 60 percent of people with diabetes do not achieve their target blood sugar levels with their current treatment regimen.(4) In addition, 85 percent of type 2 diabetes patients are overweight and 55 percent are considered obese.(5) Data support that weight loss (even a modest amount) helps patients in their efforts to achieve and sustain glycemic control.(6,7)

Important Safety Information for BYETTA

BYETTA improves glucose (blood sugar) control in adults with type 2 diabetes. It is used with metformin, a sulfonylurea, or a thiazolidinedione. BYETTA is not a substitute for insulin in patients whose diabetes requires insulin treatment. BYETTA is not recommended for use in patients with severe problems digesting food or those who have severe disease of the stomach or kidney.

When BYETTA is used with a medicine that contains a sulfonylurea, hypoglycemia (low blood sugar) is a possible side effect. To reduce this possibility, the dose of sulfonylurea medicine may need to be reduced while using BYETTA. Other common side effects with BYETTA include nausea, vomiting, diarrhea, dizziness, headache, feeling jittery, and acid stomach. Nausea is the most common side effect when first starting BYETTA, but decreases over time in most patients.

If patients experience the following severe and persistent symptoms (alone or in combination): abdominal pain, nausea, vomiting, or diarrhea, they should talk to their healthcare provider because these symptoms could be signs of serious medical conditions. BYETTA may reduce appetite, the amount of food eaten, and body weight. No changes in dose are needed for these side effects. These are not all of the side effects from use of BYETTA. A healthcare provider should be consulted about any side effect that is bothersome or does not go away.

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 has developed and gained approval for two first- in-class medicines for diabetes, SYMLIN(R) (pramlintide acetate) injection and BYETTA(R) (exenatide) injection. 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. Further information about Amylin Pharmaceuticals is available at www.amylin.com.

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. For more information about Lilly's current diabetes products, visit www.lillydiabetes.com.

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. Additional information about Lilly is available at www.lilly.com.

Alkermes, Inc., a biotechnology company committed to developing innovative medicines to improve patients' lives, manufactures RISPERDAL(R) CONSTA(R) for schizophrenia and developed and manufactures VIVITROL(R) for alcohol dependence. 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 BYETTA and the revenues generated from BYETTA 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 BYETTA 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 SEC 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.

P-LLY

(1) The International Diabetes Federation Diabetes Atlas.

(2) "All About Diabetes." American Diabetes Association.

(3) "Direct and Indirect Costs of Diabetes in the United States." American Diabetes Association.

(4) Saydah SH, Fradkin J and Cowie CC. "Poor Control of Risk Factors for Vascular Disease Among Adults with Previously Diagnosed Diabetes." JAMA: 291(3), January 21, 2004.

(5) Bays HE, Chapman RH, Grandy S. The relationship of body mass index to diabetes mellitus, hypertension and dyslipidaemia: comparison of data from two national surveys. Int J Clin Pract. 2007;61:737-47.

(6) Nutrition Recommendations and Interventions for Diabetes: a position statement of the American Diabetes Association. Diabetes Care. 2007;30 Suppl 1:S48-65

(7) Anderson JW, Kendall CW, Jenkins DJ. Importance of weight management in type 2 diabetes: review with meta-analysis of clinical studies. J Am Coll Nutr. 2003;22:331-9

Posted: June 2008

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