After One Year, Type 2 Diabetes Patients Taking Exenatide Once Weekly Sustained Improvements in Glycemic Control and Weight; DURATION-1 Presented at ADA 2008

Phase 3 Once Weekly Investigational Diabetes Therapy Also Improved Glucose

Control in Patients Switching from Exenatide Taken Twice a Day

Jun 09, 2008, 01:00 ET from Eli Lilly and Company

    SAN FRANCISCO, June 9 /PRNewswire-FirstCall/ -- 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 [A1C: -2.0%+/-0.08; fasting plasma glucose (FPG) -47+/-3
 mg/dL] compared to those receiving treatment for 30 weeks [A1C change from
 baseline: -1.9%+/-0.08 (LS mean+/-SE)]. This study also showed that
 patients who switched from BYETTA(R) (exenatide) injection after 30 weeks
 to exenatide once weekly experienced additional improvements in A1C and
 fasting plasma glucose. Seventy-four percent of all patients in the study
 achieved an endpoint A1C of 7 percent or less at 52 weeks. Patients in both
 treatment groups experienced a statistically significant and sustained
 average weight loss of 9.5 pounds over 52 weeks. 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.
     "Diabetes is a lifelong condition that requires constant management of
 blood glucose or blood sugar as well as weight. In DURATION-1 trial,
 patients significantly reduced their blood glucose levels and, on average,
 lost a total of over nine pounds. 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."
     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+/-44lbs., 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.
 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 BYETTA 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 A1C and fasting plasma glucose levels at week 52 [A1C: -2.0%+/-0.1; FPG
 -47+/-3 mg/dL (LS mean+/-SE)]. Patients who switched from BYETTA to
 exenatide once weekly had further improvements in glycemic control [A1C:
 -2.0% +/-0.1; FPG - 43+/-3 mg/dL] 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 glycemic control.
     In both groups, A1C reduction was similar at 52 weeks. Seventy-two
 percent of patients treated with exenatide once weekly achieved an endpoint
 A1C of 7 percent or less, and 54 percent achieved an A1C of 6.5 percent or
 less. In patients who switched from BYETTA to exenatide once weekly, 75
 percent of patients achieved an endpoint A1C of 7 percent or less and 53
 percent achieved an A1C of 6.5 percent or less. An A1C of below 7 percent
 is the target for good glucose control as recommended by the ADA. Unlike
 the weight gain that is commonly associated with insulin therapy and many
 oral diabetes medications, exenatide once weekly was associated with an
 average weight loss of 9.5 pounds 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.
     Safety Profile
     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
 hypoglycemia events regardless of background therapy, were observed with
 exenatide once weekly. 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 exenatide once weekly patients.
 Patients switching from BYETTA to exenatide once weekly did not experience
 a significant increase in nausea following the transition. 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 thiazolidinedione, and progressive weight loss. BYETTA was
 approved in April 2005 and has been used by approximately one million
 patients since its introduction. For full prescribing information, visit
     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) supports 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.
     For full prescribing information, visit
     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
     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,
     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
     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
     (1) The International Diabetes Federation Diabetes Atlas. Available at:
 . Accessed June 2, 2008.
     (2) "All About Diabetes." American Diabetes Association. Available at: Accessed June 2, 2008.
     (3) "Direct and Indirect Costs of Diabetes in the United States."
 American Diabetes Association. Available at:
     Accessed June 2, 2008.
     (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
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SOURCE Eli Lilly and Company