FDA Licenses Diabetes Drug Alogliptin, in 3 Formulations

Miriam E. Tucker


January 25, 2013

The US Food and Drug Administration has approved 3 different formulations of the selective dipeptidyl peptidase IV inhibitor alogliptin for the treatment of type 2 diabetes.

On January 25, the FDA announced approval of 3 drugs — Nesina (alogliptin) tablets, the fixed-dose combinations Kazano (alogliptin and metformin hydrochloride) tablets, and Oseni (alogliptin and pioglitazone) tablets for use with diet and exercise to improve blood glucose control in adults with type 2 diabetes. All 3 are manufactured by Takeda Pharmaceuticals America, Inc.

Alogliptin is a selective dipeptidyl peptidase IV inhibitor (DPP-4) that works by slowing the inactivation of incretin hormones GLP-1 (glucagon-like peptide-1) and GIP (glucose-dependent insulinotropic peptide) involved in regulating blood glucose levels.

The FDA had rejected Takeda's previous application for alogliptin in July 2009, citing insufficient cardiovascular data. The company resubmitted applications for both alogliptin and the alogliptin/pioglitazone combination in July 2011, but in April 2012, the FDA requested further data.

The current approval is based on data from separate studies for all 3 formulations. Alogliptin monotherapy was studied in 14 clinical trials involving 8500 patients with type 2 diabetes, in whom it produced hemoglobin A1c reductions of 0.4 to 0.6 percentage points at 26 weeks compared with placebo.

The FDA is requiring 5 postmarketing studies for alogliptin, including 3 pediatric studies, a cardiovascular outcomes trial, and an enhanced pharmacovigilance program to monitor for liver abnormalities, serious cases of pancreatitis, and severe hypersensitivity reactions.

The alogliptin/metformin combination was studied in 4 clinical trials involving over 2500 patients. It produced A1c reductions of 1.1 percentage points over alogliptin alone, and 0.5 percentage points over metformin at 26 weeks. As with metformin monotherapy, it will carry a black-box warning about the risk for lactic acidosis. Two postmarketing studies will be required for this formulation.

For alogliptin/pioglitazone, 4 clinical trials involving more than 1500 patients produced additional A1c reductions of 0.4 to 0.6 percentage points over pioglitazone monotherapy, and 0.4 to 0.9 percentage points over alogliptin alone. As with the other 2, the FDA is requiring enhanced pharmacovigilance for severe adverse events. And, as with pioglitazone, it will carry a black-box warning for heart failure.

Alogliptin will now be the fourth DPP-IV inhibitor licensed in the United States, but it was supposed to be the first. It was already far along in development in 2008 when the FDA issued new cardiovascular safety requirements for all new diabetes medications. This meant that Takeda had to start fresh with new trials, while 3 competitors that were further back in development — sitagliptin (Januvia, Merck), saxagliptin (Onglyza, AstraZeneca and Bristol-Myers Squibb), and linagliptin (Tradjenta, Boehringer Ingelheim and Lilly) — were able to beat alogliptin to market.