The FINANCIAL — Amylin Pharmaceuticals, Inc. (Nasdaq: AMLN), Eli Lilly and Company (NYSE: LLY), and Alkermes, Inc. (Nasdaq: ALKS) announced results from a 30-week study that compared the efficacy of exenatide once weekly, a long-acting release formulation of exenatide, to BYETTA (exenatide) injection.
Type 2 diabetes patients treated with exenatide once weekly, an investigational therapy, showed statistically significant improvements in A1C (-1.9%+/-0.08 (LS mean+/-SE)) and fasting plasma glucose (FPG -42+/-3 mg/dL) from baseline and compared with BYETTA (-1.5%+/-0.08, A1C and -25+/-3 mg/dL, FPG). Patients in both treatment groups also reported significant weight loss (average of 8 pounds) and 77 percent of patients treated with exenatide once weekly achieved an A1C of 7 percent or less. These findings were presented at the 68th Annual Scientific Sessions of the American Diabetes Association (ADA) in San Francisco.
BYETTA is indicated as adjunctive therapy to improve glycemic control in patients with type 2 diabetes mellitus who are taking metformin, a sulfonylurea, a thiazolidinedione, a combination of metformin and a sulfonylurea, or a combination of metformin and a thiazolidinedione but have not achieved adequate glycemic control.
"We know that a substantial number of type 2 diabetes patients are overweight, and conventional diabetes therapies, while controlling blood glucose, may have little or no beneficial impact on body weight. Importantly, the DURATION-1 results suggested the significant, beneficial impact of continuous levels of exenatide once weekly on glycemic control, and additionally, weight loss," said Daniel J. Drucker, M.D., Professor in the Division of Endocrinology, Department of Medicine, of Toronto, Director of the Banting and Best Diabetes Centre.
Study Design and Findings
The Diabetes Therapy Utilization: Researching Changes in A1C, Weight and Other Factors Through Intervention with Exenatide ONce Weekly (DURATION-1) study was a 30-week, randomized, open-label study of 295 patients with type 2 diabetes (baseline values: A1C 8.3%+/-1.0, FPG 169+/-43 mg/dL, weight 225+/-44 lbs., BMI 35+/-5.0 kg/m2, diabetes duration 6.7+/-5.0 years; mean+/-SD) who were treated with exenatide once weekly 2.0 mg or BYETTA twice daily as outlined in the approved label subcutaneously. Patients in both groups who completed the randomized portion of the study continued in an open-ended portion of the study to receive exenatide once weekly. Patients in both treatment arms showed improvements in A1C from baseline. In addition, treatment with exenatide once weekly resulted in statistically significant reductions in A1C [A1C change from baseline: 1.9%+/-0.08] compared to BYETTA [A1C change from baseline: 1.5%+/-0.08 (P=0.002)].
Seventy-seven percent of patients treated with exenatide once weekly achieved an A1C of 7 percent or less versus 61 percent for BYETTA (P=0.004). The ADA-recommended target for good glucose control is an A1C of below 7 percent. For patients entering the study with a baseline A1C of 9 percent or greater, at endpoint, 29 percent of patients treated with exenatide once weekly achieved A1C levels of 6.5 percent or less versus 13 percent for BYETTA. Both BYETTA and exenatide once weekly treatment groups showed significant glycemic improvements irrespective of baseline A1C.
Treatment with exenatide once weekly also resulted in significant lowering of FPG concentrations (reductions of -42+/-3 mg/dL, exenatide once weekly; – 25+/-3 mg/dL, BYETTA, P<0.0001 vs. BYETTA). Unlike the weight gain that is commonly associated with insulin therapy and many oral diabetes medications, both BYETTA and exenatide once weekly were associated with an average weight loss of 8 pounds.
In addition to weight loss, patients treated with exenatide once weekly experienced the following effects on several cardiovascular risk factors, including total cholesterol (total cholesterol -11.9+/-2.3 mg/dL from baseline 173 mg/dL; LDL -4.9+/-2.0 mg/dL from baseline 91.6 mg/dL; HDL -0.9+/-0.6 mg/dL from baseline 43.9 mg/dL) and triglycerides (15 percent improvement of mean ratio of week-30 to baseline from a baseline of 166.0 mg/dL).
Exenatide once weekly uses a proprietary technology for long-acting medications developed by Alkermes. The technology encapsulates active medication into polymer-based microspheres that are injected into the body where they degrade slowly, gradually releasing the drug in a controlled manner to provide continuous therapeutic exenatide concentrations.
Safety Profile
Exenatide once weekly was well tolerated with nearly 90 percent of patients completing 30 weeks of treatment. There were no major hypoglycemia events regardless of background therapy. Cases of minor hypoglycemia with exenatide once weekly and with BYETTA use were limited to patients using background sulfonylurea therapy. In both groups, nausea was predominantly mild and transient and occurred less frequently in the exenatide once weekly patients. Twenty-six percent of patients receiving exenatide once weekly reported nausea during the 30-week study. The antibody profiles of patients treated in this study were consistent with the previously reported profiles of BYETTA and exenatide once weekly. These data further supported the known safety profile of the exenatide molecule.
