Takeda Pharmaceuticals North America, maker of the thiazolidinedione (TZD) pioglitazone, has resubmitted new drug applications (NDA) in hopes of gaining approval from the FDA for alogliptin, an investigative dipeptidyl peptidase IV inhibitor (DPP-4i) to treat type 2 diabetes, and a fixed-dose combination therapy alogliptin/pioglitazone.
The FDA will review Takeda’s NDAs within the next six months. While pioglitazone (Actos) was approved in 1999 to treat type 2 diabetes as an adjunct to diet and exercise, alogliptin is a DPP-4i that is under investigational use for the same indication.
Alogliptin slows the inactivation of incretin hormones glucagon-like peptide-1 and glucose-dependent insulinotropic peptide, which regulate blood glucose levels.
Takeda submitted the NDA with interim results from the EXAMINE (EXamination of CArdiovascular OutcoMes: AlogliptIN vs. Standard of CarE in Patients with Type 2 Diabetes Mellitus and Acute Coronary Syndrome) trial, a randomized, double-blind, placebo-controlled outcomes study to evaluate cardiovascular endpoints comparing alogliptin and standard care versus standard care alone.
The trial enrolled type 2 diabetes patients with recent acute coronary syndromes (ACS), and the Deerfield, Ill.-based company said that the final trial results are expected in 2014.
Takeda has conducted 12 Phase III clinical trials involving alogliptin that have enrolled more than 8,000 patients at more than 1,000 centers. During the studies, researchers evaluated the safety and efficacy of alogliptin as a once-daily monotherapy adjunct to diet and exercise, and as an add-on therapy to other antidiabetic medications, like metformin.
Use of a 25mg once-daily dose of alogliptin significantly reduced hemoglobin A1c levels. Additionally, nearly 3,000 patients were enrolled in a study evaluating the combination alogliptin/pioglitazone. The researchers found that glycemic control was significantly improved when the drug combination was administered.
Recently, both France and Germany pulled pioglitazone off the shelves after research originating in France showed that pioglitazone may increase the risk of bladder cancer when diabetics are administered the drug. The FDA also revised pioglitazone’s warning label to indicate that when the drug is taken for more than a year, patients may have an increased risk of bladder cancer.
Earlier this month the Japanese Ministry of Health, Labour and Welfare approved an NDA for the combination alogliptin/pioglitazone to treat type 2 diabetes.