Month: June 2010

MAPLE GROVE, Minn., June 28 /PRNewswire-AsiaNet/ —

Second Deal in Six Months Expands CNS Portfolio to Four Programs

Upsher-Smith Laboratories, Inc. today announced an agreement with Ikano Therapeutics, Inc. to obtain exclusive global rights to ITI-111, Ikano’s nasal midazolam. Under terms of the agreement, Upsher-Smith will assume all further development, testing and clinical study of nasal midazolam as an orphan drug for the management of acute repetitive seizure (ARS) in patients with epilepsy. Upon successful completion of development and regulatory approval, Upsher-Smith will commercialize the product, initially in the U.S. market.

“Currently, epilepsy patients experiencing cluster seizures or acute repetitive seizures have limited options for treatment,” said Dr. Jacqueline French, Professor of Neurology at the New York University Comprehensive Epilepsy Center. “A product such as nasal midazolam could represent an additional treatment option for these patients, and has the potential to address a significant unmet need.”

Some patients with epilepsy periodically experience episodes of ARS that are distinct from their usual seizure pattern. There have been no new FDA-approved products targeting ARS in nearly 15 years.(1)

“The addition of nasal midazolam to our growing development portfolio represents a significant milestone in helping us achieve our vision of building a leadership position in the central nervous system field,” said Mark Evenstad, President of Upsher-Smith. “We will continue to focus our efforts on the development of products that address significant unmet needs for patients with epilepsy, Parkinson’s disease and Alzheimer’s disease.”

Upsher-Smith’s development programs for the management of epilepsy include USL255 (extended-release topiramate) and tonabersat. USL255 is an internally developed program that recently entered a Phase III clinical trial for the adjunctive treatment of partial onset seizures in adults. USL255 is designed to provide convenient once-daily dosing and reduce fluctuations in topiramate blood levels observed with currently available immediate-release topiramate options. Tonabersat is a first-in-class neuronal gap junction modulator that may have applicability in a variety of neurological conditions, including migraine and epilepsy.

About Epilepsy and Acute Repetitive Seizures (ARS)
Epilepsy is a neurological condition that produces seizures affecting a variety of mental and physical functions.

ARS may be defined as a predictable component of a patient’s seizure disorder which is historically distinct from the patient’s other seizures in type, frequency, severity or duration with an onset which is easily recognized by the patient’s family and physician.(2) An ARS episode may last from minutes to hours and may have a consistent, predictable component such as an aura or prodrome which is temporally linked to subsequent seizures. Episodes of ARS may progress to prolonged seizure or status epilepticus in some patients and may diminish the function and quality of life for both patients and their families.(2)

About Upsher-Smith
Upsher-Smith Laboratories, Inc., founded in 1919, is a rapidly growing, privately held pharmaceutical company that manufactures and markets branded and branded generic prescription and over-the-counter products. Upsher-Smith’s product portfolio focuses in the areas of women’s health, dermatology, cardiology, and central nervous system diseases. The company’s growing CNS pipeline concentrates on diseases with significant unmet need, including epilepsy, Parkinson’s disease, and Alzheimer’s disease. Its leading CNS products in development are USL255 (extended-release topiramate) and tonabersat for epilepsy, and PRX1 for the symptomatic treatment of Parkinson’s disease. To expand its CNS pipeline, Upsher-Smith seeks alliances and co-development programs, pursues licensing and acquisitions, and leverages the development of its core competency in formulation development. For more information, visit http://www.upsher-smith.com.

About Ikano Therapeutics Inc.
Ikano Therapeutics Inc. (ITI) is a specialty pharmaceutical company focused on developing innovative specialty therapeutics, with an emphasis on drugs in areas for which there is proven, unsatisfied medical and patient need. ITI’s goal is to apply formulation and development expertise across selected therapeutic areas to create new and differentiated products that improve safety, efficacy and clinical utility for patients, caregivers and health care professionals. For more information, please visit the ITI web site at http://www.ikanotherapeutics.com.

1. Martin J. Acute repetitive seizures and seizure emergencies: weighing your treatment options. March 3, 2005. Accessed 6/1/10 at http://www.epilepsy.com/articles/ar_1109872672.

2. Cereghino JJ. Identification and treatment of acute repetitive seizures in children and adults. Curr Treat Options Neurol. 2007 Jul; 9(4):249-55.

SOURCE Upsher-Smith Laboratories, Inc.

CONTACT: Daina Cardillo,
Kovak-Likly Communications,
+1-203-762-8833,
dcardillo@klcpr.com

ORLANDO, Fla., June 26 /PRNewswire-AsiaNet/ —

Study Presented at ADA 2010

Amylin Pharmaceuticals, Inc. (Nasdaq: AMLN) and Eli Lilly and Company (NYSE: LLY) today announced results from the first double-blind, placebo-controlled clinical study to evaluate exenatide injection added to insulin glargine, which showed patients with type 2 diabetes achieved glucose targets without weight gain or increasing their risk of hypoglycaemia. These findings were presented at the 70th Annual Scientific Sessions of the American Diabetes Association (ADA) in Orlando, Fla.

In the study, patients receiving insulin glargine, with or without oral agents, were randomized to receive exenatide or placebo in addition to aggressive insulin titration. After 30 weeks of treatment, HbA1c decreased by 1.7 percentage points in patients adding exenatide, compared with a decrease of 1.0 percentage point in patients treated with insulin alone. Weight decreased in patients adding exenatide by 1.81 kilograms, compared with an increase of 0.90 kilograms in patients treated with insulin alone. Fasting plasma glucose and hypoglycaemia were similar between treatment groups.

“Even in this population of patients who were poorly controlled on insulin therapy, the addition of exenatide to optimized basal insulin therapy provided exactly what we hoped for – improved control of blood sugar throughout the day, weight loss and no increased risk of hypoglycaemia as compared to optimized basal insulin treatment alone,” said John 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. “This study showed exenatide may provide a complementary addition to basal insulin for these hard-to-treat type 2 diabetes patients.”

Exenatide is not currently approved for this dosing regimen. Results from this study will form the basis for a supplemental New Drug Application (sNDA) to the U.S. Food and Drug Administration (FDA). The filing is planned for the end of 2010.

Study Design and Findings
The double-blind, placebo-controlled study enrolled 261 patients (mean age: 59 years old; weight: 93.89 kilograms; HbA1c: 8.4 percent; diabetes duration: 12 years; insulin dose 48 units) who were randomized to exenatide 10 micrograms (n=137) or placebo (n=122). Groups were generally comparable at baseline. Insulin dose was decreased by 20 percent if a patient’s HbA1c was 8 percent for five weeks, then titrated to achieve a target fasting glucose of <5.55 mmol/l. Primary endpoint was change in HbA1c, a measure of average blood sugar over three months. Continuous glucose monitoring (n=23) and 7-point glucose profiles demonstrated significant postprandial effects with exenatide compared with insulin alone. Insulin dose increased more in the placebo group (20 +/- 2 units) than in the exenatide group (13 +/- 2 units) to achieve the fasting glucose target.

Safety Profile
Overall, nausea was the most common event during the 30-week treatment period and decreased over time. Nausea occurred in 41 percent of patients treated with exenatide compared with 8 percent of patients treated with insulin alone. Hypoglycaemia was similar for both groups; major hypoglycaemia occurred twice in one patient receiving insulin alone.

About Diabetes
It is estimated that by 2010, diabetes will affect 284.6 million adults worldwide and more than 55.4 million in Europe.(i, ii) 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.(iii)

Type 2 diabetes usually occurs in adults over the age of 40, but is increasingly common in younger people.(iv) In virtually every high-income country, diabetes is ranked among the leading causes of blindness, renal failure and lower limb amputation as well as one of the leading causes of death, largely because of a markedly increased risk of coronary heart disease and stroke (cardiovascular disease).(v) In the European region, estimates indicate that at least 106 billion USD will be spent on healthcare for diabetes in 2010, accounting for 28 percent of global expenditure.(vi)

About exenatide Injection
Exenatide was the first 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.(vii) 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 sulfonylurea, two common oral diabetes medications. Since the U.S. market introduction in June 2005, more than one million patients worldwide have been treated with exenatide.

Important Safety Information for exenatide
In clinical studies, the most common side effects were hypoglycaemia (low blood sugar) when taken with a sulfonylurea, 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 Amylin and Lilly
Amylin Pharmaceuticals is a biopharmaceutical company dedicated to improving lives of patients 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. Further information on Amylin Pharmaceuticals is available at www.amylin.com.

Through a long-standing commitment to diabetes care, Lilly seeks to provide patients with breakthrough treatments that enable them to live longer, healthier and fuller lives. Since 1923, Lilly has been an 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 pharmaceutical products by applying the latest research from its own worldwide laboratories and from collaborations with eminent scientific organizations. Headquartered in Indianapolis, Ind., 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.

This press release contains forward-looking statements about Amylin and Lilly. 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/or the revenues generated from exenatide, may be affected by competition; unexpected new data; safety and technical issues; the study results mentioned in this press release not being predictive of real-world results; clinical trials not being completed in a timely manner, not confirming previous results, not being predictive of real-world use, or not achieving the intended clinical endpoints; label expansion requests not 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 development and commercialization of pharmaceutical products, including those inherent in the collaboration with and dependence upon Amylin and/or Lilly. These and additional risks and uncertainties are described more fully in Amylin’s and Lilly’s most recent SEC filings, including their Quarterly Reports on Form 10-Q and Annual Reports on Form 10-K. Amylin and Lilly undertake no duty to update these forward-looking statements.

BYETTA(R) is a registered trademark of Amylin Pharmaceuticals, Inc. All other marks are the marks of their respective owners.

(i) The International Diabetes Federation Diabetes Atlas. Available at: http://www.diabetesatlas.org/content/regional-overview. Accessed on June 9,2010.
(ii) The International Diabetes Federation Diabetes Atlas. Available at: http://www.diabetesatlas.org/content/europe. Accessed on June 9, 2010.
(iii) 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.
(iv) The International Diabetes Federation Diabetes Atlas. Available at http://www.diabetesatlas.org/content/what-is-diabetes. Accessed on June 9,2010.
(v) The International Diabetes Federation Diabetes Atlas. Available at http://www.diabetesatlas.org/content/what-is-diabetes. Accessed on June 9,2010.
(vi) The International Diabetes Federation Diabetes Atlas. Available at: http://www.diabetesatlas.org/content/europe. Accessed on June 9,2010.
(vii) 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.

SOURCE: Eli Lilly and Company

CONTACT: Amylin – Anne Erickson
+1-858-754-4443
Cell: +1-858-349-3195
anne.erickson@amylin.com; or

Lilly – Tim Coulom
+1-317-655-2998
Cell: +1-317-544-9757
Email: coulomtd@lilly.com

ORLANDO, Fla., June 26 /PRNewswire-AsiaNet/ —

Study Showed Improvements Compared to Insulin Glargine

Amylin Pharmaceuticals, Inc. (Nasdaq: AMLN) and Eli Lilly and Company (NYSE: LLY) today announced results from a study comparing the effect of long-term treatment with either exenatide injection or insulin glargine on overall beta-cell function. (Beta cells are cells in the pancreas that produce insulin.) Three years of exenatide therapy improved indices of beta-cell function assessed four weeks after discontinuing therapy. These findings were presented at the 70th Annual Scientific Sessions of the American Diabetes Association (ADA) in Orlando, Fla.

After three years of treatment, both therapies reduced HbA1c similarly (by 0.7 percentage points to 6.6 percent for exenatide and by 0.5 percentage points to 6.9 percent for insulin glargine). HbA1c is a measure of average blood sugar over three months. In addition, exenatide significantly reduced body weight compared to insulin glargine (7.7 kilogram difference between groups). After completion of three years of therapy, a four-week off-drug period followed to allow assessment of parameters of metabolic state including beta-cell function. Beta-cell function was assessed using a calculated disposition index (insulin secretion adjusted for insulin sensitivity). Exenatide increased insulin sensitivity by 39 percent and increased the disposition index, indicating an improvement in background beta-cell function. Insulin glargine had no effect on insulin sensitivity or disposition index.

“Type 2 diabetes is a progressive disease in which insulin production typically decreases over time,” said Michaela Diamant, M.D., professor of diabetology, director, Diabetes Center VUMC, Amsterdam, the Netherlands, and principal investigator of the study. “These findings suggest that with extended use, exenatide treatment may help improve insulin production and help people with type 2 diabetes control their blood sugar levels.”

Study Design and Findings
In the first portion of the study, metformin-treated patients with type 2 diabetes were randomized to receive exenatide (n=36) or insulin glargine (n=33) and measures of beta-cell function, blood sugar control and weight change were compared. Baseline characteristics were age 59 +/- years; HbA1c 7.5 +/- 0.8 percent; BMI 31 +/- 4 kg/m2; weight 91.6 +/- 13.1 kilograms. One-year study results, previously published in Diabetes Care, found that patients receiving exenatide, compared to those treated with insulin glargine, showed significant improvements in beta-cell function. However, the improvements were not sustained following an initial four-week off-drug period.

In this study, a total of 46 patients entered the two-year open-label extension period, and 36 completed the study (exenatide n=16; insulin glargine n=20). Insulin sensitivity and beta-cell function were assessed at baseline and after a second four-week off-drug period, following a total of three years of treatment. To assess beta-cell function, an estimate of insulin secretion (first-phase glucose stimulated C-peptide secretion) was measured. This measurement was adjusted for insulin sensitivity in the calculated disposition index. Both therapies reduced HbA1c similarly (to 6.6 +/- 0.2 percent and 6.9 +/- 0.2 percent for exenatide and insulin glargine, respectively) after three years of treatment. After the four-week off-drug period, the disposition index was increased in the exenatide-treated group compared to baseline (+1.43 +/- 0.78). The disposition index was reduced with insulin glargine (-0.99 +/- 0.65). In addition, exenatide increased insulin sensitivity by 39 percent, while insulin glargine treatment showed no effect. Thus, both insulin sensitivity and beta-cell function were improved after exenatide therapy for three years.

About Diabetes
It is estimated that by 2010, diabetes will affect 284.6 million adults worldwide and more than 55.4 million in Europe.(i, ii) 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.(iii)

Type 2 diabetes usually occurs in adults over the age of 40, but is increasingly common in younger people.(iv) In virtually every high-income country, diabetes is ranked among the leading causes of blindness, renal failure and lower limb amputation as well as one of the leading causes of death, largely because of a markedly increased risk of coronary heart disease and stroke (cardiovascular disease).(v) In the European region, estimates indicate that at least 106 billion USD will be spent on healthcare for diabetes in 2010, accounting for 28 percent of global expenditure.(vi)

About exenatide Injection
Exenatide was the first 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(vii). 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 sulfonylurea, two common oral diabetes medications. Since the U.S. market introduction in June 2005, more than one million patients worldwide have been treated with exenatide.

Important Safety Information for exenatide
In clinical studies, the most common side effects were hypoglycaemia (low blood sugar) when taken with a sulfonylurea, 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 Amylin and Lilly
Amylin Pharmaceuticals is a biopharmaceutical company dedicated to improving lives of patients 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. Further information on Amylin Pharmaceuticals is available at www.amylin.com.

Through a long-standing commitment to diabetes care, Lilly seeks to provide patients with breakthrough treatments that enable them to live longer, healthier and fuller lives. Since 1923, Lilly has been an 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 pharmaceutical products by applying the latest research from its own worldwide laboratories and from collaborations with eminent scientific organizations. Headquartered in Indianapolis, Ind., 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.

This press release contains forward-looking statements about Amylin and Lilly. 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/or the revenues generated from exenatide, may be affected by competition; unexpected new data; safety and technical issues; the study results mentioned in this press release not being predictive of real-world results; clinical trials not being completed in a timely manner, not confirming previous results, not being predictive of real-world use, or not achieving the intended clinical endpoints; label expansion requests not 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 development and commercialization of pharmaceutical products, including those inherent in the collaboration with and dependence upon Amylin and/or Lilly. These and additional risks and uncertainties are described more fully in Amylin’s and Lilly’s most recent SEC filings, including their Quarterly Reports on Form 10-Q and Annual Reports on Form 10-K. Amylin and Lilly undertake no duty to update these forward-looking statements.

BYETTA(R) is a registered trademark of Amylin Pharmaceuticals, Inc. All other marks are the marks of their respective owners.

(i) The International Diabetes Federation Diabetes Atlas. Available at: http://www.diabetesatlas.org/content/regional-overview. Accessed on June 9,2010.
(ii) The International Diabetes Federation Diabetes Atlas. Available at: http://www.diabetesatlas.org/content/europe. Accessed on June 9,2010.
(iii) 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.
(iv) The International Diabetes Federation Diabetes Atlas. Available at http://www.diabetesatlas.org/content/what-is-diabetes. Accessed on June 9,2010.
(v) The International Diabetes Federation Diabetes Atlas. Available at http://www.diabetesatlas.org/content/what-is-diabetes. Accessed on June 9,2010.
(vi) The International Diabetes Federation Diabetes Atlas. Available at: http://www.diabetesatlas.org/content/europe . Accessed on June 9,2010.
(vii) 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.

SOURCE: Eli Lilly and Company

CONTACT: Amylin – Anne Erickson
+1-858-754-4443
Cell: +1-858-349-3195
Email: anne.erickson@amylin.com; or

Lilly – Tim Coulom
+1-317-655-2998
Cell: +1-317-544-9757
coulomtd@lilly.com

ORLANDO, Fla., June 26 /PRNewswire-AsiaNet/ —

Data from Nearly 1,100 Patients in DURATION-1, -2 and -3 Trials Showed
Exenatide Once Weekly was Well-Tolerated

Amylin Pharmaceuticals, Inc. (Nasdaq: AMLN), Eli Lilly and Company (NYSE: LLY) and Alkermes, Inc. (Nasdaq: ALKS) today announced results of an analysis of pooled safety data from three completed randomized controlled trials that showed the investigational product exenatide once weekly, dosed once weekly, was generally well-tolerated with a low discontinuation rate due to serious adverse events similar to pooled comparators in patients with type 2 diabetes. BYDUREON(TM) is the proposed brand name for exenatide once weekly in the United States. These findings were presented at the 70th Annual Scientific Sessions of the American Diabetes Association (ADA) in Orlando, Fla.

Safety data from the DURATION-1, -2 and -3 trials involving patients on either exenatide once weekly or pooled data from comparator groups including sitagliptin, pioglitazone HCI or insulin glargine were analyzed. The overall incidence rates of adverse events (AEs), serious AEs and discontinuations due to serious AEs were similar for exenatide once weekly versus pooled comparators. AEs occurred in 77 percent of patients receiving exenatide once weekly versus 71 percent for pooled comparators; serious AEs were 4 percent for exenatide once weekly versus 5 percent for pooled comparators; and discontinuations due to serious AEs were less than 1 percent for both groups. Discontinuation for nausea was similar in exenatide once weekly (0.7 percent) and pooled comparator (0.5 percent) cohorts. Hypoglycaemic events were lower with exenatide once weekly, and composite exposure-adjusted incidence rates were similar for exenatide once weekly versus pooled comparators for pancreatitis, gall-bladder AEs, renal impairment / dehydration and thyroid-neoplasm AEs.

In the DURATION-1, -2 and -3 studies there were no reports of severe hypersensitivity reactions, such as serious skin reactions or anaphylaxis. These data further support the known safety profile of the exenatide molecule and are consistent with the previously reported profiles of exenatide once weekly and BYETTA(R) (exenatide) injection.

“The DURATION trials not only help us understand the potential of exenatide once weekly in improving blood glucose control as measured by HbA1c, but also its safety and tolerability,” said Orville G. Kolterman, M.D., senior vice president, chief medical officer, Amylin Pharmaceuticals. “Overall, these data showed that exenatide once weekly was generally well-tolerated with a low discontinuation rate due to serious adverse events, adding to the potential of exenatide once weekly as a desirable treatment option for type 2 diabetes in just one dose per week.”

Exenatide once weekly is an investigational, extended-release medication for type 2 diabetes designed to deliver continuous therapeutic levels of exenatide in a single weekly dose. Exenatide once weekly is a once-weekly formulation of exenatide, the active ingredient in exenatide twice daily, which has been available in the U.S. since June 2005 and in Europe since 2007 and is used in more than 60 countries worldwide to improve glycaemic control in adults with type 2 diabetes. Exenatide once weekly and exenatide belong to the glucagon-like peptide-1 (GLP-1) receptor agonist class of medications.

Study Design and Findings
This analysis of the DURATION-1, -2 and -3 trials included 1,095 patients followed for 26 to 30 weeks on either exenatide once weekly (n=541) or pooled comparators (sitagliptin, pioglitizone and insulin glargine; n=554). Selected analyses compared the exenatide once weekly cohort to patients receiving exenatide in the DURATION-1 trial (n=145). Baseline demographics of cohorts were similar and were approximately 50 percent male; mean age 52-58 years; mean HbA1c 8.3-8.5 percent; and mean BMI 32-35 kg/m2.

Common treatment-emergent AEs (>/= 5 percent) that differed between exenatide once weekly and pooled comparator cohorts were injection-site pruritis and gastrointestinal (GI), including nausea, vomiting, diarrhea and constipation. The comparator-corrected incidence of nausea was 15 percent for exenatide once weekly. After three months, at which point a steady-state level of exenatide is reached, approximately 1 percent of subjects treated with exenatide once weekly reported new nausea. Other GI AEs included dyspepsia / reflux symptoms. Abdominal discomfort (2 percent) also was seen in exenatide once weekly and pooled comparator cohorts.

To further understand differences in the tolerability profile of exenatide once weekly and exenatide, the incidence of GI adverse events for the exenatide once weekly cohort was compared to that of exenatide. Nausea was reported more often by exenatide recipients (35 percent) than exenatide once weekly recipients (20 percent). Similarly, vomiting was reported by 19 percent of exenatide recipients compared with 8 percent of exenatide once weekly recipients.

Local injection-site pruritis (itchiness) (7 percent) and erythema (redness) (4 percent) were also observed with exenatide once weekly. The incidence of mild to moderate hypoglycaemic events observed with exenatide once weekly treatment (16 percent) was lower compared to the pooled comparator cohort (22 percent). There were no events of major hypoglycaemia. One death unrelated to assigned treatment was observed in each group. Composite exposure-adjusted cases (per 100 patient-years) were similar for exenatide once weekly versus pooled comparator, respectively, for pancreatitis (0.4 vs. 0.8), gall-bladder AEs (0.8 vs. 2.0), renal impairment / dehydration (1.2 vs. 1.2) and thyroid-neoplasm AEs (0.4 vs. 0.4).

About Diabetes
It is estimated that by 2010, diabetes will affect 284.6 million adults worldwide and more than 55.4 million in Europe(i,ii). 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(iii).

Type 2 diabetes usually occurs in adults over the age of 40, but is increasingly common in younger people(iv). In virtually every high-income country, diabetes is ranked among the leading causes of blindness, renal failure and lower limb amputation as well as one of the leading causes of death, largely because of a markedly increased risk of coronary heart disease and stroke (cardiovascular disease)(v). In the European region, estimates indicate that at least 106 billion USD will be spent on healthcare for diabetes in 2010, accounting for 28 percent of global expenditure(vi).

About exenatide Injection
Exenatide was the first 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(vii). 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 sulfonylurea, two common oral diabetes medications. Since the U.S. market introduction in June 2005, more than one million patients worldwide have been treated with exenatide.

Important Safety Information for exenatide
In clinical studies, the most common side effects were hypoglycaemia (low blood sugar) when taken with a sulfonylurea, 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 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 Medisorb(R) technology for long-acting medications. Exenatide once weekly is not currently approved by any regulatory agencies.

Amylin Pharmaceuticals is a biopharmaceutical company dedicated to improving lives of patients 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.

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 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 fully integrated biotechnology company committed to developing innovative medicines to improve patients’ lives. Alkermes’ robust pipeline includes extended-release injectable and oral products for the treatment of prevalent, chronic diseases, such as central nervous system disorders, addiction and diabetes. Headquartered in Waltham, Massachusetts, Alkermes has a research facility in Massachusetts and a commercial manufacturing facility in 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 once weekly may not be approved by the FDA or in the EU in a timely manner or at all; the companies’ response to the complete response letter may not satisfy the FDA; the FDA may request additional information prior to approval; exenatide and/or the approval of exenatide once weekly and the revenues generated from these products may be affected by competition; unexpected new data; safety and technical issues; clinical trials not being completed in a timely manner, not confirming previous results, not being predictive of real world use or not achieving the intended clinical endpoints; label expansion requests or NDA filings, such as the NDA filing for exenatide once weekly mentioned in this press release, not receiving regulatory approval; the commercial launch of exenatide once weekly being delayed; or manufacturing and supply issues. The potential for exenatide and/or exenatide once weekly 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 development and commercialization of pharmaceutical products including those inherent in the collaboration with and dependence upon Amylin, Lilly and/or Alkermes. These and additional risks and uncertainties are described more fully in Amylin’s, Lilly’s and Alkermes’ most recent SEC filings including their Quarterly Reports on Form 10-Q and Annual Reports on Form 10-K. Amylin, Lilly and Alkermes undertake no duty to update these forward-looking statements.

BYDUREON(TM) and BYETTA(R) are trademarks of Amylin Pharmaceuticals, Inc., and Medisorb(R) is a registered trademark of Alkermes, Inc. All other marks are the marks of their respective owners.

(i) The International Diabetes Federation Diabetes Atlas. Available at: http://www.diabetesatlas.org/content/regional-overview. Accessed on June 9,2010.
(ii) The International Diabetes Federation Diabetes Atlas. Available at: http://www.diabetesatlas.org/content/europe. Accessed on June 9,2010.
(iii) 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.
(iv) The International Diabetes Federation Diabetes Atlas. Available at http://www.diabetesatlas.org/content/what-is-diabetes. Accessed on June 9,2010.
(v) The International Diabetes Federation Diabetes Atlas. Available at http://www.diabetesatlas.org/content/what-is-diabetes. Accessed on June 9,2010.
(vi) The International Diabetes Federation Diabetes Atlas. Available at: http://www.diabetesatlas.org/content/europe. Accessed on June 9,2010.
(vii) 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.

SOURCE: Eli Lilly and Company

CONTACT: Amylin – Anne Erickson
Phone: +1-858-754-4443
Cell: +1-858-349-3195
Email: anne.erickson@amylin.com

Lilly – Tim Coulom
Phone: +1-317-655-2998
Cell: +1-317-544-9757
Email: coulomtd@lilly.com

Alkermes – Rebecca Peterson
Phone: +1-781-609-6378
Cell: +1-617-899-2447
Email: rebecca.peterson@alkermes.com