Takeda receives FDA approval for EDARBYCLOR to treat hypertension

Takeda Pharmaceutical Company Limited (Takeda) and its wholly-owned subsidiary, Takeda Pharmaceuticals North America, Inc., announced that the U.S. Food and Drug Administration (FDA) approved EDARBYCLOR (azilsartan medoxomil and chlorthalidone) for the treatment of hypertension to lower blood pressure in adults. EDARBYCLOR is the only fixed-dose therapy in the U.S. to combine an angiotensin II receptor blocker (ARB) with the diuretic chlorthalidone in a once-daily, single tablet. The recommended starting dose of EDARBYCLOR is 40/12.5 mg and the maximum dose is 40/25 mg.

The two medications in EDARBYCLOR work to help lower blood pressure in patients with hypertension. Azilsartan medoxomil, marketed as EDARBI in the U.S., reduces blood pressure by blocking the action of angiotensin II, a vasopressor hormone that naturally exists within the body. When EDARBI blocks the angiotensin II receptor, blood vessels can stay relaxed and open, and blood pressure can be reduced. Chlorthalidone reduces the amount of water in the body by increasing the flow of urine, which helps to lower blood pressure. Prior landmark clinical outcomes trials have demonstrated that chlorthalidone is effective in reducing blood pressure in patients with hypertension and that long-term use is associated with reductions in serious hypertension-related complications.

"Hypertension is a complex disease that affects one in three Americans. It is critical to control hypertension because lowering blood pressure has been shown to reduce the risk of serious health consequences, including stroke and heart attack," said Domenic Sica, M.D., professor of internal medicine and nephrology at Virginia Commonwealth University Medical Center. "The approval of EDARBYCLOR provides an effective treatment option to lower blood pressure for appropriate patients with hypertension who may require a combination of drugs to help achieve blood pressure goals."

Takeda Global Research & Development Center, Inc. U.S. submitted the new drug application for EDARBYCLOR in February 2011. The overall clinical program consisted of five phase 3 clinical studies involving more than 5,000 patients with hypertension. The studies, evaluating the safety and efficacy of EDARBYCLOR, ranged from eight weeks to 52 weeks in duration, with doses of azilsartan medoxomil/chlorthalidone ranging from 20/12.5 to 80/25 mg once daily. The studies demonstrated EDARBYCLOR:

• Lowered mean trough (22-24 hours) systolic blood pressure (SBP) by Ambulatory Blood Pressure Monitoring significantly more than either azilsartan medoxomil or chlorthalidone alone
• Lowered blood pressure in black and non-black patients at similar levels
• Lowered clinic SBP significantly more than the fixed-dose combination of olmesartan medoxomil-hydrochlorothiazide at its highest approved dose (40/25 mg doses for both medications)

The most common adverse reactions seen in clinical studies were dizziness and fatigue.

"In clinical studies, EDARBYCLOR demonstrated statistically significant blood pressure reductions compared to its respective monotherapies and was shown to be superior to the fixed-dose combination of olmesartan medoxomil and hydrochlorothiazide at maximum respective doses," said Paulos Berhanu, M.D., executive medical director of medical & scientific affairs at Takeda. "It is our belief this innovative treatment helps reinforce Takeda's family of cardiovascular therapies by providing a new option to help appropriate patients, regardless of age, gender or race, work toward reaching their blood pressure goals."