September 12, 2013

Takeda and Allergan Announce a Licensing Agreement for EDARBI and EDARBYCLOR

Takeda and Allergan enter into a license, development and commercialization agreement for EDARBI (azilsartan medoxomil) and EDARBYCLOR (azilsartan medoxomil and chlorthalidone) in the U.S.

Deerfield, Ill., Osaka, Japan, and Atlanta, September 12, 2013 – Takeda Pharmaceutical Company Limited (Takeda) and Allergan Pharmaceuticals Ireland Ltd., a wholly-owned subsidiary of Allergan Pharmaceuticals, LLC ("Allergan") announced today that Takeda and Allergan have entered into a license, development and commercialization agreement. It will provide Allergan with exclusive rights to market and sell EDARBI (azilsartan medoxomil) and EDARBYCLOR (azilsartan medoxomil and chlorthalidone) in the U.S. market effective September 12, 2013.

Under the terms of the agreement, Allergan will have exclusive rights to promote and sell EDARBI and EDARBYCLOR in the United States. In return, Takeda will receive an upfront payment along with a series of future milestone and royalty payments based upon sales of the EDARBI family of products.

"This is an opportunity to capture the value that we've created in developing and launching the EDARBI family of products while positioning us to optimize our commercial resources to support our recent and anticipated launches of new products," said Douglas Cole, president, Takeda Pharmaceuticals U.S.A., Inc. "We are pleased to entrust the EDARBI family in the United States to Allergan who will continue to ensure EDARBI products are available as a treatment option to patients with hypertension. Takeda maintains its global commitment to find new therapies and expand upon the cardiovascular metabolic franchise. The EDARBI family of products remains a priority for a variety of Takeda's markets globally."

"We are excited about our acquisition of U.S. rights to EDARBI and EDARBYCLOR and look forward to representing these important brands to patients and healthcare providers," said Ed Schutter, president & CEO of Allergan. "As a specialty pharmaceutical company already focused in the cardiovascular area, we are well-positioned to ensure the EDARBI products are available to all appropriate patients who may need them."

About Hypertension

Hypertension, or high blood pressure, is a chronic medical condition in which blood pressure is elevated to 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 blood pressure in individuals with severe hypertension can provide substantial benefit.

Hypertension impacts approximately 67 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 is approved in the United States, Canada, Europe and Mexico.

EDARBYCLOR (azilsartan medoxomil and chlorthalidone) is a fixed-dose combination therapy for the treatment of hypertension that combines azilsartan medoxomil and chlorthalidone in a single tablet. Chlorthalidone reduces the amount of water in the body by increasing the flow of urine, which helps lower blood pressure. EDARBYCLOR is indicated for the treatment of hypertension to lower blood pressure in adults; it may be used in patients not adequately controlled with monotherapy and as an initial therapy if a patient is likely to need multiple drugs to achieve blood pressure goals. The recommended starting dose of EDARBYCLOR in adults is 40/12.5 mg taken orally once daily. The maximal dose is 40/25 mg.

Important Safety Information

WARNING: FETAL TOXICITY. See full Prescribing Information for complete boxed warning. When pregnancy is detected, discontinue EDARBI or EDARBYCLOR as soon as possible. Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus.

EDARBYCLOR is contraindicated in patients with anuria.

Do not coadminister aliskiren with EDARBI or EDARBYCLOR in patients with diabetes.

Fetal Toxicity: Use of drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death. When pregnancy is detected, discontinue EDARBI or EDARBYCLOR as soon as possible. Thiazides cross the placental barrier and appear in cord blood and may be associated with adverse reactions, including fetal or neonatal jaundice and thrombocytopenia.

In patients with an activated renin-angiotensin-aldosterone system (RAAS), such as volume- and/or salt-depleted patients, EDARBI and EDARBYCLOR can cause excessive hypotension. Correct volume or salt depletion prior to administration of EDARBI or EDARBYCLOR.

Monitor for worsening renal function in patients with renal impairment. In patients whose renal function may depend on the activity of the renin-angiotensin system, treatment with ACE inhibitors and ARBs has been associated with oliguria or progressive azotemia and rarely with acute renal failure and death. In patients with renal artery stenosis, EDARBI and EDARBYCLOR may cause renal failure. In patients with renal disease, chlorthalidone may precipitate azotemia; consider withholding or discontinuing EDARBYCLOR if progressive renal impairment becomes evident. Avoid use of aliskiren with EDARBI or EDARBYCLOR in patients with renal impairment (GFR <60 mL/min).

Hypokalemia is a dose-dependent adverse reaction that may develop with chlorthalidone. Coadministration of digitalis may exacerbate the adverse effects of hypokalemia. EDARBYCLOR attenuates chlorthalidone-associated hypokalemia.

Hyperuricemia may occur or frank gout may be precipitated in certain patients receiving chlorthalidone or other thiazide diuretics.

Adverse Reactions (AEs):

  • The most common AE that occurred more frequently with EDARBI than placebo in adults was diarrhea (2% vs 0.5%).
  • AEs that occurred at an incidence of >=2% of EDARBYCLOR-treated patients and greater than azilsartan medoxomil or chlorthalidone were dizziness (8.9%) and fatigue (2.0%).

Incidence of consecutive elevations of creatinine with EDARBYCLOR (>=50% from baseline and >ULN) was 2% and were typically transient, or nonprogressive and reversible, and associated with large blood pressure reductions. With EDARBI 80 mg, small reversible increases were seen.

Drug Interactions:

  • Renal clearance of lithium is reduced by diuretics, such as chlorthalidone, increasing the risk of lithium toxicity.
  • Monitor renal function periodically in patients receiving EDARBI or EDARBYCLOR and NSAIDs who are also elderly, volume-depleted (including those on diuretics), or who have compromised renal function, as deterioration of renal function, including possible acute renal failure, may result. These effects are usually reversible. NSAIDs may interfere with antihypertensive effect.
  • Dual blockade of the RAS with angiotensin receptor blockers, ACE inhibitors, or aliskiren is associated with increased risks of hypotension, hyperkalemia, and changes in renal function (including acute renal failure) compared to monotherapy.

Please click here for complete EDARBI Prescribing Information or here for complete EDARBYCLOR Prescribing Information.

Indications and Usage

EDARBI and EDARBYCLOR are indicated for the treatment of hypertension to lower blood pressure. EDARBI is an angiotensin II receptor blocker (ARB) and EDARBYCLOR is an ARB and a thiazide-like diuretic combination. EDARBYCLOR may be used if a patient is not adequately controlled on monotherapy or as initial therapy if multiple drugs are needed to help achieve blood pressure goals. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. There are no controlled trials demonstrating risk reduction with EDARBI or EDARBYCLOR, but trials with chlorthalidone and at least one pharmacologically similar drug to azilsartan medoxomil have demonstrated such benefits.

Control of high blood pressure should be part of comprehensive cardiovascular risk management, including, as appropriate, lipid control, diabetes management, antithrombotic therapy, smoking cessation, exercise, and limited sodium intake. Many patients will require more than one drug to achieve blood pressure goals.

EDARBI and EDARBYCLOR may be used with other antihypertensive agents.

About Allergan Pharmaceuticals

Allergan Pharmaceuticals Ireland Limited is a wholly-owned subsidiary of Allergan Pharmaceuticals, LLC, a specialty pharmaceutical company headquartered in Atlanta, Georgia and currently focused on the cardiovascular, pediatric and hospital markets. The company intends to become a leading specialty pharmaceutical company by actively licensing, developing and commercializing late-stage products for specialty focused conditions. Allergan currently markets multiple NDA and ANDA approved products with several more filed or in development. For more information regarding Allergan Pharmaceuticals or any of its products, visit www.Allerganpharm.com or send email inquiries to info@Allerganpharm.com.