BYETTA-basal insulin combination therapy receives EMA CHMP positive opinion

Amylin Pharmaceuticals, Inc. (Nasdaq: AMLN) and Eli Lilly and Company (NYSE: LLY) today announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has issued a positive opinion in the European Union (EU) for the expanded use of BYETTA® (exenatide twice-daily) as an add-on therapy to basal insulin, with or without metformin and/or Actos® (pioglitazone), for the treatment of type 2 diabetes in adults who have not achieved adequate glycemic control with these agents. The CHMP's decision is now referred for final action to the European Commission, which has the authority to approve medicines for the EU. The Commission usually decides on CHMP recommendations within two to three months.

"The combination of BYETTA with basal insulin has potential as a complementary treatment approach for several reasons," said Christian Weyer, M.D., senior vice president, research and development, Amylin Pharmaceuticals. "BYETTA is given in a fixed-dose regimen. Its effects contribute to improved glycemic control after meals, complementing the control of fasting blood sugar achieved with basal insulin. And in a clinical study, patients using BYETTA with insulin glargine achieved better glycemic control, without weight gain or an increased risk of hypoglycemia, than patients using insulin glargine without BYETTA."

The double-blind clinical trial evaluating BYETTA as an add-on therapy to insulin glargine was published in Annals of Internal Medicine. In the 30-week study, BYETTA 10 micrograms or placebo was added to existing insulin glargine therapy (with or without metformin, pioglitazone or both), which was titrated to achieve target fasting glucose levels. At study entry, patients who may have been at increased risk of hypoglycemia (A1C less than or equal to 8 percent) reduced their dose of insulin glargine by 20 percent. Five weeks after randomization, all patients had insulin doses titrated to achieve target fasting glucose levels. The primary endpoint was reduction in A1C, a measure of average blood sugar over three months; secondary endpoints included change in body weight along with other parameters of glucose control, cardiovascular health, hypoglycemia and patient-reported outcomes.

After 30 weeks of treatment, BYETTA demonstrated a statistically significant reduction in A1C compared to placebo, lowering A1C by 1.7 percentage points from a baseline of 8.3 percent. Patients treated with optimized insulin glargine plus placebo experienced a 1.0 percentage point decrease in A1C from a baseline of 8.5 percent. Patients who added BYETTA to their insulin glargine regimen saw their weight decrease by an average of 4 pounds, compared with an increase of 2 pounds in patients who were treated with optimized insulin glargine plus placebo. BYETTA is not indicated for the management of obesity and weight loss was a secondary endpoint in the trial. Fasting glucose change and hypoglycemia incidence were similar between treatment groups.

Thirteen BYETTA recipients and one placebo recipient (9 percent vs. 1 percent) discontinued the study because of adverse events (p less than 0.010); rates of nausea (41 percent vs. 8 percent), diarrhea (18 percent vs. 8 percent), vomiting (18 percent vs. 4 percent), headache (14 percent vs. 4 percent) and constipation (10 percent vs. 2 percent) were higher with BYETTA than with placebo. Hypoglycemia was similar for both groups; major hypoglycemia occurred twice in one patient receiving insulin glargine without BYETTA.

In November 2011, Lilly and Amylin announced that they amicably terminated their decade-long collaboration. As part of the transition plan outside the U.S., Amylin will assume responsibility for exenatide product commercialization efforts on a market-by-market basis by the end of 2013. Amylin will work with Lilly on plans for markets outside the U.S. during the transition period. Amylin intends to provide uninterrupted patient supply in all markets where exenatide products are launched, as well as additional markets in the future. Both companies are committed to ensuring a seamless transition of global product responsibility to Amylin while maintaining continuity of patient care. Amylin anticipates working with one or more partners outside the U.S. in order to maximize the global potential of this innovative molecule and achieve greater operational flexibility and efficiency.