Takeda has resubmitted two New Drug Applications (NDA) to the U.S. Food and Drug Administration (FDA) for alogliptin and the fixed-dose combination therapy alogliptin/pioglitazone, which combines alogliptin with pioglitazone, approved in 1999, for the treatment of type 2 diabetes, in a single tablet.
Alogliptin is a selective DPP-4i (dipeptidyl peptidase IV inhibitor) under investigation in the U.S. for the treatment of type 2 diabetes as an adjunct to diet and exercise. DPP-4 inhibitors address insulin deficiency by slowing the inactivation of incretin hormones GLP-1 (glucagon-like peptide-1) and GIP (glucose-dependent insulinotropic peptide). As a result, an increased amount of active incretins enables the pancreas to secrete insulin, in a glucose-dependent manner, thereby assisting in the management of blood glucose levels.
The NDA resubmissions include interim results from the EXAMINE study, a cardiovascular outcomes trial requested by the FDA to satisfy the criteria outlined in the December 2008 “Guidance for Industry: Diabetes Mellitus — Evaluating Cardiovascular Risk in New Antidiabetic Therapies to Treat Type 2 Diabetes.” The EXAMINE study was designed to comply with the Guidance. This randomized, double-blind, placebo-controlled outcomes study continues to evaluate cardiovascular endpoints following treatment with alogliptin in addition to standard of care, versus standard of care alone, in patients with type 2 diabetes and a recent acute coronary syndrome (ACS). Final study results are expected in 2014.
The FDA will review the NDA resubmissions within the next six months.
An NDA for alogliptin was approved in April 2010 by the Japanese Ministry of Health, Labour, and Welfare for the treatment of type 2 diabetes.
Pioglitazone, marketed as Actos in the U.S., may be associated with an increased risk of bladder cancer. In June the FDA announced it would require this information to be added to the Warnings and Precautions label of medicines containing pioglitazone.