Takeda Pharmaceutical Company Limited (Takeda) has announced that Takeda Global Research & Development Center, Inc. submitted a New Drug Application (NDA) to the United States Food and Drug Administration (FDA) for alogliptin (development code: SYR-322), a highly selective dipeptidyl peptidase-4 (DPP-4) inhibitor under investigation for the treatment of type 2 diabetes.
Discovered by Takeda San Diego, Inc., alogliptin was designed to selectively inhibit DPP-4 taken orally once daily.
DPP-4 inhibitors are a new class of oral agents for the treatment of type 2 diabetes, which slow the inactivation of incretin hormones GLP-1 (glucagon-like peptide-1) and GIP (glucose-dependent insulinotropic peptide). The incretins play a major role in regulating blood glucose levels and may have the potential to improve pancreatic beta-cell function.
The NDA submission was supported by six Phase 3 clinical trials involving over 2,000 patients conducted in 220 centers worldwide. The safety and efficacy of alogliptin was studied as a once-daily monotherapy adjunct to diet and exercise and as an add-on therapy to other antidiabetic medications including sulfonylureas, metformin, thiazolidinediones (TZDs), and insulin. In the studies, alogliptin was associated with statistically significant reductions in hemoglobin A1c, which reflects average blood glucose concentration over the previous two to three months. Alogliptin was generally well-tolerated and weight neutral. There was no increase in hypoglycemia compared to placebo.
“The NDA submission for alogliptin is a significant milestone for Takeda, as it has the potential to position us as one of the global leaders in diabetes treatment,” said Yasuchika Hasegawa, president of Takeda. “Takeda's continued growth, now and in the future, will be based on our ability to focus and have success in this therapeutic area. Our hope is that alogliptin will become an important treatment option for patients with type 2 diabetes and the healthcare providers who treat them.”
GLP-1 and GIP are produced by the digestive tract in response to food, and regulate glucose balance, primarily by stimulating glucose-dependent insulin secretion. In addition, GLP-1 suppresses pancreatic glucagon secretion and subsequent liver glucose production, enhances glucose disposal, slows gastric emptying, and elicits satiety, a feeling of fullness.
Type 2 diabetes has reached epidemic proportions in the United States with almost 20 million people currently living with the disease. A progressive disease, type 2 diabetes requires continued monitoring by a physician and patients are often required to take multiple medications at any time—in addition to diet and exercise—in order to maintain glucose control. There are two primary defects associated with type 2 diabetes: the body does not efficiently use the insulin it produces—insulin resistance—and/or it does not produce enough insulin—insulin deficiency. DPP-4 inhibitors offer a new way to treat insulin deficiency and have the potential to improve pancreatic beta-cell function.
Takeda has a long-standing tradition of striving toward better health for people living with type 2 diabetes by developing innovative pharmaceutical solutions to help manage their condition. In 1999, Takeda launched ACTOS® (pioglitazone HCl) — an insulin sensitizer which today is available globally — followed in recent years by the introduction of the ACTOS family of products, with more than 75 million prescriptions written, covering more than 8.5 million patients and 4.5 million patient years.