Meta-Analysis of SYMLIN(R) Clinical Data Showed No Increased Risk of Cardiovascular Adverse Events Associated With SYMLIN Treatment in Patients With Type 2 Diabetes

ORLANDO, Fla., June 26, 2010 /PRNewswire-FirstCall/ -- Amylin Pharmaceuticals, Inc. (Nasdaq: AMLN) today announced results from an analysis of an integrated database of clinical studies that showed no increased risk of cardiovascular (CV) events associated with SYMLIN® (pramlintide acetate) injection use compared to a pooled comparator group treated with either placebo or rapid-acting insulin. These findings were presented at the 70th Annual Scientific Sessions of the American Diabetes Association (ADA) in Orlando, Fla.

The meta-analysis included five completed, randomized, controlled clinical trials of 16 to 52 weeks' duration, and was based on the U.S. Food and Drug Administration's (FDA's) recent guidance for evaluating CV risk in new type 2 diabetes agents. The primary endpoint for this analysis was occurrence of primary major adverse CV events (MACE). The 95 percent confidence interval for the estimated risk ratio for the primary endpoint was 0.55 to 1.34.  With the upper limit below the FDA-specified threshold of 1.8, this suggests that there is no increase in CV risk associated with SYMLIN use.  

"People with diabetes are two to four times more likely to develop cardiovascular disease because of increased risk factors such as high blood pressure, lipid disorders and obesity," said Orville G. Kolterman, M.D., senior vice president, chief medical officer at Amylin. "SYMLIN is an important tool for many patients who struggle to achieve their glucose control targets, despite their best efforts with insulin. These safety analyses confirm our findings from individual clinical studies and provide additional insight into the CV safety profile of SYMLIN use in type 2 diabetes."

Study Design and Findings

In this integrated analysis, 1,434 SYMLIN subjects and 582 pooled comparator subjects were treated for a total of 957 and 359 patient-years of exposure, respectively. Subjects in both groups received at least one type of insulin, and in some cases, oral antidiabetic agents. The mean age (56-57 years), body mass index (32-33 kg/m2), and blood sugar as measured by A1C, a measure of average blood sugar over three months, (9.0-9.1 percent) were comparable between the treatment groups.

The primary endpoint was occurrence of primary major adverse CV events (MACE), including CV mortality, myocardial infarction, stroke, acute coronary syndrome hospitalization, and urgent revascularization procedures. The relative risk between the SYMLIN and pooled comparator groups was 0.86 (95 percent confidence interval: 0.55–1.34). The hazard ratios for primary MACE ranged from 0.88 to 0.93, depending on the analysis method (95 percent confidence interval: 0.56–1.38). Additional analyses of narrower and broader MACE definitions resulted in similar findings with the upper limit of the 95 percent confidence interval below 1.8 for most CV endpoints and analysis methods. These data suggest that SYMLIN treatment in patients with type 2 diabetes is not associated with an increased risk of CV adverse events.

The findings from this meta-analysis are further supported by an analysis of post-marketing reports, which have not revealed evidence of a signal for CV risk in an estimated cumulative exposure of 67,540 patient-years since the launch of SYMLIN in 2005.

About Diabetes

Diabetes affects more than 24 million people in the United States and an estimated 285 million adults worldwide.(i,ii) It is a complex metabolic disease manifesting with a defect in the beta cells in the pancreas, resulting in a deficiency of both insulin and amylin secretion. 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 $174 billion per year in direct and indirect medical expenses.(iii)

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.(iv) In addition, 85 percent of type 2 diabetes patients are overweight and 55 percent are considered obese.(v) Data support that weight loss (even a modest amount) supports patients in their efforts to achieve and sustain glycemic control.(vi,vii)

About SYMLIN

Taken at mealtime, SYMLIN is the first and only amylin mimetic for use in patients with diabetes treated with mealtime insulin. SYMLIN is a synthetic analog of human amylin, a naturally occurring hormone that is made in the beta cells of the pancreas, the same cells that make insulin. In patients with type 2 diabetes who use insulin, and in patients with type 1 diabetes, those cells in the pancreas are either damaged or destroyed, resulting in reduced secretion of both insulin and amylin after meals. The use of SYMLIN contributes to glucose control after meals.

The SymlinPen® (pramlintide acetate) pen-injector is an easy way for patients to use SYMLIN and offers convenient pre-filled SYMLIN administration with simple, dial-up dosing to improve mealtime glucose control. The SymlinPen®120 features fixed dosing to deliver 60 or 120 micrograms of SYMLIN per dose. The SymlinPen®60 features fixed dosing to deliver 15, 30, 45, or 60 micrograms of SYMLIN per dose.

Healthcare professionals and patients with diabetes may obtain more information, including the complete Prescribing Information and the Medication Guide, at www.SYMLIN.com.

Important Safety Information for SYMLIN

SYMLIN is not intended for all patients with diabetes. SYMLIN is used with insulin and has been associated with an increased risk of insulin-induced severe hypoglycemia, particularly in patients with type 1 diabetes. When severe hypoglycemia associated with SYMLIN use occurs, it is seen within three hours following a SYMLIN injection. If severe hypoglycemia occurs while operating a motor vehicle, heavy machinery, or while engaging in other high-risk activities, serious injuries may occur. Appropriate patient selection, careful patient instruction, and insulin dose adjustments are critical elements for reducing this risk.

Other adverse events commonly observed with SYMLIN when co-administered with insulin were mostly gastrointestinal in nature, including nausea, which was the most frequently reported adverse event. The incidence of nausea was higher at the beginning of SYMLIN treatment and decreased with time in most patients. The incidence and severity of nausea are reduced when SYMLIN is gradually increased to the recommended doses.

About Amylin Pharmaceuticals

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® (pramlintide acetate) injection and BYETTA® (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 http://www.amylin.com.

This press release contains forward-looking statements about Amylin, which involve risks and uncertainties. The Company's actual results could differ materially from those discussed due to a number of risks and uncertainties, including that our clinical trials may not start when planned and/or confirm previous results; the meta-analysis described in this press release may not be predictive of real world experience; our product candidates may not receive regulatory approval; and inherent scientific, regulatory and other risks in the drug development and commercialization process; SYMLIN and the SymlinPen, and the revenues generated from these products, may be affected by competition, unexpected new data, technical or safety issues, or manufacturing and supply issues. Commercial and government reimbursement and pricing decisions and the pace of market acceptance may also affect the potential for SYMLIN and the SymlinPen. These and additional risks and uncertainties are described more fully in the Company's most recently filed SEC documents, including its Form 10-Q. Amylin undertakes no duty to update these forward-looking statements.

(i) Diabetes Statistics. American Diabetes Association. Available at http://www.diabetes.org/diabetes-basics/diabetes-statistics/. Accessed June 19, 2010.

(ii) The International Diabetes Federation Diabetes Atlas. Available at: http://www.diabetesatlas.org/content/some-285-million-people-worldwide-will-live-diabetes-2010. Accessed June 19, 2010.

(iii) Direct and Indirect Costs of Diabetes in the United States. American Diabetes Association. Available at: http://www.diabetes.org/how-to-help/action/resources/cost-of-diabetes.html. Accessed June 19, 2010.

(iv) Saydah SH, Fradkin J and Cowie CC. Poor control of risk factors for vascular disease among adults with previously diagnosed diabetes. JAMA. 2004;291:335-42.

(v) 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.

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

(vii) 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.

SOURCE Amylin Pharmaceuticals, Inc.