FDA Approves EDARBYCLOR (azilsartan medoxomil and chlorthalidone) for the Treatment of Hypertension

DEERFIELD, Ill. and OSAKA, Japan, Dec. 20, 2011 /PRNewswire/ -- Takeda Pharmaceutical Company Limited (Takeda) and its wholly-owned subsidiary, Takeda Pharmaceuticals North America, Inc., announced today 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."

About Hypertension
Hypertension, or high blood pressure, is a chronic medical condition in which blood pressure is elevated at levels of 140 mm Hg or greater systolic and/or 90 mm Hg or greater diastolic. Elevated systolic or diastolic pressure causes increased cardiovascular risk, and the absolute risk increase per mm Hg is greater at higher blood pressures, so that even modest reductions of severe hypertension can provide substantial benefit. Hypertension impacts approximately 75 million Americans, or nearly one in three adults. It is estimated that nearly one billion people are affected by hypertension worldwide, and this figure is predicted to increase to 1.5 billion by 2025. Hypertension typically has no symptoms. Adults of all ages and backgrounds can develop hypertension; however, the risk of developing the condition increases with age, with more than half of people over age 60 affected. Hypertension is also costly to the nation's health care system. The American Heart Association recently estimated that direct and indirect expenses associated with hypertension cost the nation more than $73 billion in 2009.

About EDARBI and EDARBYCLOR
EDARBI (azilsartan medoxomil) is an angiotensin II receptor blocker (ARB) developed by Takeda for the treatment of hypertension to lower blood pressure in adults. EDARBI lowers blood pressure by blocking the action of angiotensin II, a vasopressor hormone, which 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. EDARBI is indicated for the treatment of hypertension to lower blood pressure in adults, either alone or in combination with other antihypertensive agents. The recommended dose of EDARBI in adults is 80 mg taken once daily. A starting dose of 40 mg may be appropriate for patients on high doses of diuretics. EDARBI recently received Marketing Authorization in Europe and is currently available in the United States and Mexico.