Takeda Resubmits New Drug Applications in the U.S. for Investigational Type 2 Diabetes Therapies Alogliptin and the Fixed-Dose Combination Alogliptin/Pioglitazone

DEERFIELD, Ill. and OSAKA, Japan, July 25, 2011 /PRNewswire/  -- Takeda Pharmaceutical Company Limited (Takeda) announced today that Takeda Global Research & Development Center, Inc., resubmitted two New Drug Applications (NDA) to the United States (U.S.) Food and Drug Administration (FDA) for alogliptin and the fixed-dose combination therapy alogliptin/pioglitazone, which combines alogliptin with pioglitazone in a single tablet. The FDA will review the NDA resubmissions within the next six months. Pioglitazone was approved in 1999 for the treatment of type 2 diabetes as an adjunct to diet and exercise. Alogliptin is a selective dipeptidyl peptidase IV inhibitor (DPP-4i) under investigation in the U.S. for the treatment of type 2 diabetes as an adjunct to diet and exercise. Discovered by Takeda San Diego, Inc., alogliptin is designed to slow the inactivation of incretin hormones GLP-1 (glucagon-like peptide-1) and GIP (glucose-dependent insulinotropic peptide), which play a role in regulating blood glucose levels.

"We believe interim results from a cardiovascular outcomes trial satisfy the FDA's cardiovascular safety requirements to allow the Agency to complete its review of our NDA, and further support the product profile of alogliptin," said David Recker, M.D., senior vice president, clinical science, Takeda Global Research & Development Center. "If approved, alogliptin/pioglitazone will be the first type 2 diabetes treatment option in the U.S. to include both a DPP-4 inhibitor and a thiazolidinedione in a single tablet."

The NDA resubmissions include 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) 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 NDA resubmissions mark a significant milestone for Takeda in the U.S., underscoring our deeply held commitment to providing therapeutic options for patients living with type 2 diabetes," said Robert Spanheimer, M.D., vice president, medical and scientific affairs, Takeda Pharmaceuticals North America. "We are confident in the data available for alogliptin, and look forward to building upon our global expertise in the diabetes therapeutic area."

Phase 3 Clinical Program

Twelve phase 3 clinical trials of alogliptin involving more than 8,000 patients were conducted in over 1,000 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 several other classes of antidiabetic medications, including metformin, thiazolidinediones (TZDs), insulin and sulfonylureas. In these studies, alogliptin 25 mg, taken once daily, demonstrated statistically significant reductions in hemoglobin A1c, which reflects average blood glucose concentration over the previous two to three months. The common adverse events (greater than or equal to 5% and greater than placebo) identified in this phase 3 program include headache, urinary tract infection, nasopharyngitis, and upper respiratory tract infection.

Of the 8,000 patients, the alogliptin/pioglitazone studies included more than 3,000 patients. Study results indicated that alogliptin/pioglitazone produced significant improvements in glycemic control. The common adverse events (greater than or equal to 5% and greater than placebo) identified in this phase 3 program include nasopharyngitis, back pain, urinary tract infection, and influenza.

About Type 2 Diabetes

Type 2 diabetes is the most common form of diabetes and has reached epidemic proportions globally. Almost 26 million Americans currently live with diabetes, and at least seven million are unaware that they have it. Type 2 diabetes is a progressive and chronic condition and patients should work with a health care professional to manage and monitor their disease. In addition to diet and exercise, patients often need to take multiple medications in order to help manage blood glucose control. The global health care expenditures to treat and prevent diabetes and its complications were estimated at $376 billion in 2010. By 2030, this number is projected to exceed $490 billion.

About Alogliptin and Alogliptin/Pioglitazone

Alogliptin is a DPP-4i being investigated, as an adjunct to diet and exercise, for the treatment of type 2 diabetes. 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. 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.  

Alogliptin/pioglitazone is a fixed-dose combination therapy in development for the treatment of type 2 diabetes, which combines alogliptin and pioglitazone in a single tablet. Pioglitazone is a TZD that directly targets insulin resistance, a condition in which the body does not efficiently use the insulin it produces to control blood glucose levels, and is approved in adults for the treatment of type 2 diabetes as an adjunct to diet and exercise. An NDA for the alogliptin/pioglitazone fixed-dose combination was approved in July 2011 by the Japanese Ministry of Health, Labour and Welfare for the treatment of type 2 diabetes.

Takeda Pharmaceuticals North America, Inc. and Takeda Global Research & Development Center, Inc.

Based in Deerfield, Ill., Takeda Pharmaceuticals North America, Inc. and Takeda Global Research & Development Center, Inc. are subsidiaries of Takeda Pharmaceutical Company Limited, the largest pharmaceutical company in Japan. The respective companies currently market oral diabetes, insomnia, rheumatology, and gastroenterology and cardiovascular treatments and seek to bring innovative products to patients through a pipeline that includes compounds in development for metabolic and cardiovascular disease, gastroenterology, neurology and other conditions. To learn more about these Takeda companies, visit www.tpna.com.

Takeda Pharmaceutical Company Limited

Located in Osaka, Japan, Takeda is a research-based global company with its main focus on pharmaceuticals. As the largest pharmaceutical company in Japan and one of the global leaders of the industry, Takeda is committed to strive towards better health for patients worldwide through leading innovation in medicine. Additional information about Takeda is available through its corporate website, www.takeda.com.

SOURCE Takeda Pharmaceutical Company Limited