Clinical study results show no increased risk of CV events associated with SYMLIN injection

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.