Takeda Announces Acceptance of European Medicines Agency Submissions for Two Fixed-Dose Combination Therapies, Alogliptin and Pioglitazone and Alogliptin and Metformin, for the Treatment of Type 2 Diabetes

LONDON and OSAKA, Japan, June 19, 2012 /PRNewswire/ --

Takeda Pharmaceutical Company Limited (Takeda) Ltd. today announced that Takeda Global Research & Development Centre (Europe) Ltd. ("TGRD Europe") received confirmation of the acceptance of submissions of Marketing Authorisation Applications (MAAs) from the European Medicines Agency (EMA) for alogliptin and pioglitazone, which combines alogliptin with pioglitazone in a single tablet, and alogliptin and metformin, which combines alogliptin with metformin in a single tablet. The EMA has confirmed that the submissions have been validated for assessment.

"Takeda has been committed to researching and developing new therapies for the type 2 diabetes population for nearly 20 years, and we are confident that these submissions are another step towards helping patients in Europe who might benefit from the right combination of treatments," said Stuart Dollow, M.D., managing director, Takeda Global Research & Development Centre (Europe) Ltd. "If approved, these two new therapies both offer the benefit of combining two medications in one, which may reduce the number of pills patients must take each day."

Alogliptin is a dipeptidyl peptidase IV inhibitor (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. Pioglitazone is a thiazolidinedione (TZD) that directly addresses 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. If approved, alogliptin and pioglitazone will be a new type 2 diabetes treatment option that includes both a DPP-4i and a TZD in a single tablet for patients in the EU.

The common adverse events (≥5%) reported in patients treated with alogliptin co-administered with pioglitazone include nasopharyngitis, back pain, urinary tract infection, and influenza.

In addition to alogliptin and pioglitazone, the EMA will also review the MAA submission for the fixed-dose combination (FDC) therapy alogliptin and metformin. Metformin is a widely used diabetes medication that acts primarily by reducing the amount of glucose produced by the liver.

Common adverse events reported in ≥5 percent of patients treated with the co-administration of alogliptin with metformin include upper respiratory tract infection, nasopharyngitis, creatinine renal clearance decreased, diarrhea, headache, hypertension, and urinary tract infection.

The MAA submission for alogliptin and pioglitazone was supported by phase 3 clinical trials involving more than 1,900 patients conducted at centers worldwide for up to one year. Study results indicated that alogliptin and pioglitazone produced significant improvements in glycemic control.

The application for alogliptin and metformin was supported by phase 3 clinical trials involving more than 4,000 patients conducted at centers worldwide for up to one year. Study results demonstrated that alogliptin co-administered with metformin produced significant improvements in glycemic control.

These submissions were also supported by data from several ongoing studies, including the EXAMINE (EXamination of CArdiovascular OutcoMes: AlogliptIN vs. Standard of CarE in Patients with Type 2 Diabetes Mellitus and Acute Coronary Syndrome) trial. Takeda is currently conducting the EXAMINE trial to evaluate cardiovascular endpoints following treatment with alogliptin, to comply with the U.S. Food and Drug Administration's (FDA) criteria outlined in the December 2008 "Guidance for Industry: Diabetes Mellitus - Evaluating Cardiovascular Risk in New Antidiabetic Therapies to Treat Type 2 Diabetes." As a company, Takeda believes the interim results from this trial meet the FDA's cardiovascular safety guideline. Final study results are expected in 2015.

About Type 2 Diabetes

Type 2 diabetes is the most common form of diabetes and has reached epidemic proportions globally. Approximately 366 million adults are currently living with type 2 diabetes worldwide, and that number continues to grow. By 2030, it is estimated that one in nine adults, or 552 million adults, will be living with the disease. The global health care expenditures to treat diabetes (both type 1 and 2) and prevent its complications were estimated at $376 billion in 2010. By 2030, this number is projected to exceed $490 billion. Because of the chronic nature of this disease, combination therapy is almost uniformly required to maintain diabetic control over many years of therapy.

About Alogliptin, Alogliptin and Pioglitazone, and Alogliptin and Metformin

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, and the therapy is currently available under the brand name NESINA^® in this market.

Alogliptin and pioglitazone is an FDC therapy in development for the treatment of type 2 diabetes, which combines alogliptin and pioglitazone in a single tablet. An NDA for the alogliptin and pioglitazone FDC was approved in July 2011 by the Japanese Ministry of Health, Labour and Welfare for the treatment of type 2 diabetes, and the therapy is currently available under the brand name LIOVEL^® in this market.

The combination therapy alogliptin and metformin includes metformin, a widely used diabetes medication that acts primarily by reducing the amount of glucose produced by the liver.

About Takeda Global Research & Development Centre (Europe) Ltd.

Based in London, England, Takeda Global Research & Development Centre (Europe), Ltd., (TGRD Europe), is a subsidiary of Takeda Pharmaceutical Company Limited, the largest pharmaceutical company in Japan. TGRD Europe seeks to bring innovative products to patients through a pipeline that includes compounds in development for diabetes, cardiovascular disease, neurology, oncology and other conditions.

About 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, http://www.takeda.com.