Amylin Pharmaceuticals Inc and Eli Lilly and Company announced that exenatide (synthetic exendin-4) produced statistically significant, dose-dependent reductions in the primary glucose control endpoint in a seven-month Phase 3 pivotal study in people with type 2 diabetes failing to achieve target blood glucose levels with metformin alone. The subjects receiving exenatide also showed statistically significant reductions in body weight. Consistent with exenatide's glucose-dependent action, no difference was observed in rates of mild to moderate hypoglycemia between the exenatide and placebo groups, and no severe hypoglycemia was observed. These results are consistent with the findings from an ongoing open-label study of exenatide recently presented at the ADA's 63rd Scientific Sessions in New Orleans, Louisiana in June 2003.
The average entry hemoglobin A1c (A1C) for subjects entering the study was 8.2 percent. A1C is a measure that reflects average glucose levels over the prior 3 to 4 month period. At the end of the study, nearly half (46%) of the participants receiving the highest dose of exenatide (10 micrograms twice daily) reduced their average glucose levels to the American Diabetes Association's (ADA) recommended target range of less than or equal to 7 percent. Subjects receiving the highest dose of exenatide ended the study with an average A1C of 7.3 percent.
The results of this first pivotal study, as well as the results from two on-going pivotal studies are intended to form the basis of a submission to the Food and Drug Administration (FDA), currently anticipated in 2004. The companies announced that no further details from this study, outside of what is discussed in this press release, will be disclosed until the results of all three pivotal trials are reported and a full analysis of the Phase 3 data is complete. The companies are on track to report the results from the remaining two pivotal trials in the fourth quarter of 2003.
"We are very encouraged by these initial pivotal results. These findings suggest that exenatide may help patients achieve and maintain optimal treatment targets," said Orville G. Kolterman, Senior Vice President, Clinical Affairs at Amylin Pharmaceuticals Inc. "If we continue to see results such as these in the other Phase 3 studies, exenatide could prove to be a valuable treatment for patients with type 2 diabetes who have difficulty reaching target glucose levels with existing treatment options."
Exenatide (synthetic exendin-4) is being investigated for its potential to address important unmet medical needs of many people with type 2 diabetes. Clinical trials suggest that exenatide treatment decreases blood glucose toward target levels and is associated with weight loss. The effects on glucose control seen with exenatide treatment are likely due to several actions that are similar to those of the naturally occurring incretin hormone GLP-1. These actions include stimulating the body's ability to produce insulin in response to elevated levels of blood glucose, inhibiting the release of glucagon following meals and slowing the rate at which nutrients are absorbed into the bloodstream.(1) In animal studies exenatide administration resulted in preservation and formation of new beta cells,(2) the insulin-producing cells in the pancreas, which fail as type 2 diabetes progresses.