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Phase 2 Data of Takeda’s Investigational GPR40 Agonist, Published in The Lancet, Demonstrated Improved Glycemic Control in Patients with Type 2 Diabetes

February 25, 2012

TAK-875 is the first GPR40 agonist to reach late-stage (Phase 3) clinical development

DEERFIELD, Ill., February 26, 2012, and OSAKA, Japan, February 27, 2012 – Phase 2 clinical data of an investigational type 2 diabetes therapy, TAK-875 of Takeda Pharmaceutical Company Limited (“Takeda”), were published online first in The Lancet. The clinical trial was conducted by Takeda’s wholly owned subsidiary, Takeda Global Research & Development Center, Inc. in Deerfield, Illinois. These data, which were presented at the American Diabetes Association 71st Annual Scientific Sessions, demonstrated that the GPR40 agonist, at doses ranging from 6.25 to 200 mg a day, met its primary endpoint of statistically significantly lowering HbA1c (blood glucose) levels over a 12-week period versus placebo. This was achieved without significant increase in the incidence of hypoglycemia (low blood sugar) compared to placebo.

Discovered by Takeda, through orphan G-protein-coupled receptors (GPCRs) research, TAK-875 is the first GPR40 agonist to reach late stage (Phase 3) clinical development, and completed studies have demonstrated glucose-lowering effects in patients with type 2 diabetes by stimulating glucose-dependent insulin secretion.

“As glucose control in many patients with type 2 diabetes continues to remain suboptimal, it is important to work to identify new mechanisms of action in an effort to improve treatment options,” said Thomas Strack, M.D., development therapeutic area head, metabolic, Takeda. “Because of its observed ability to potently stimulate insulin secretion and improve glycemic control with less or no hypoglycemia, these data further support TAK-875 as a potential therapy for the treatment of type 2 diabetes in the future.”

Agonists of GPR40, one of the GPCRs expressed in pancreatic islet cells, have a mechanism of stimulating insulin in a glucose-dependent manner, which is different from other diabetes drug classes, e.g., sulfonylureas.

“This study, published in The Lancet, demonstrated that activation of the GPR40 receptor may be beneficial in the treatment of type 2 diabetes, without significantly increasing the risk of hypoglycemia, compared to the other drug studied,” added Strack. “Takeda remains committed to developing new medications and working to improve therapeutic care. These clinical data validate the opportunity to further evaluate this different compound for the treatment of type 2 diabetes.”

About the Study
The published data included findings from a Phase 2 randomized, double-blind, placebo- and active (glimepiride) comparator-controlled, multicenter study, which was conducted to evaluate once-daily treatment with five different doses of TAK-875 (6.25 mg, 25 mg, 50 mg, 100 mg, and 200 mg), compared with placebo and glimepiride (2 mg -4 mg), over 12 weeks in type 2 diabetes patients (n=426) inadequately treated with metformin or diet and exercise alone. The primary endpoint was the change from baseline in HbA1c levels at week 12, while the secondary endpoints included fasting blood glucose, area under the curve (AUC) for glucose and insulin during an oral glucose tolerance test (OGTT), and body weight.

Study results demonstrated that all doses of TAK-875 showed significantly greater HbA1c reductions at week 12 (ranging from 0.65 percent at 6.25 mg to 1.0 percent at doses of 50 mg and higher) versus placebo, and was comparable to the HbA1c reductions with glimepiride (1.0 percent). Compared to placebo (17.6 percent), more than twice as many patients (40.4 percent) treated with 50 mg of TAK-875 achieved HbA1c less than seven percent at week 12. Only the decrease in the TAK-875 6.25 mg group was significantly smaller than that in the glimepiride group (P=0.012). The incidence of hypoglycemia was similar to placebo (3.3 percent) and significantly lower for all doses of TAK-875 (2.3 percent) compared to glimepiride (19.4 percent). Patients treated with TAK-875 had no significant impact on their body weight (-0.1 to 0.6 percent) relative to baseline in any of the dose groups, while patients receiving glimepiride experienced significant weight gain from baseline at week 12 (approximately 1.0 percent).

The overall incidence of treatment-emergent adverse events (TEAE) was similar for TAK-875 and placebo (48.7 percent versus 47.5 percent, respectively), and was higher in the glimepiride-treated group (61.3 percent). Most (>96 percent) of the TEAEs in the TAK-875 group were mild or moderate in severity. The percentage of patients with TEAEs that were considered by the investigator to be related to the blinded study drug was lowest in patients treated with TAK-875 (7.3 percent), compared with those treated with placebo (11.5 percent) and glimepiride (22.6 percent). The only TEAE reported in more than five percent of the TAK-875 group was urinary tract infection (5.3 percent), but rates for this TEAE were comparable with placebo (6.6 percent) and glimepiride (8.1 percent).

About Type 2 Diabetes
Type 2 diabetes is the most common form of diabetes and has reached epidemic proportions in the United States (U.S.). Almost 26 million Americans currently live with diabetes, and at least 7 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 medication in order to help manage glucose control. The global health care expenditures to treat diabetes and prevent its complications were estimated at $376 billion in 2010. By 2030, this number is projected to exceed $490 billion.

About TAK-875
TAK-875 is one of Takeda’s investigational therapies for type 2 diabetes. TAK-875 is a selective agonist of GPR40, one of the GPCRs that are expressed in pancreatic islet cells. This compound has a different mechanism of action for type 2 diabetes by improving glucose-dependent insulin secretion, different from sulfonylurea (such as glimepiride). Phase 3 studies have been initiated in Japan, the U.S., Latin America, and Europe.

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.

Takeda Pharmaceuticals U.S.A., Inc. and Takeda Global Research & Development Center, Inc.
Based in Deerfield, Ill., Takeda Pharmaceuticals U.S.A., 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, 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
Corporate Communications Department

Josephine Zammuto
Takeda Global Research & Development Center, Inc.
+1 (224) 554-2795
[email protected]