Takeda and Arbor Announce a Licensing Agreement for EDARBI and EDARBYCLOR

DEERFIELD, Ill. and OSAKA, Japan and ATLANTA, Sept. 12, 2013 /PRNewswire/ -- Takeda Pharmaceutical Company Limited (Takeda) and Arbor Pharmaceuticals Ireland Ltd., a wholly-owned subsidiary of Arbor Pharmaceuticals, LLC ("Arbor") announced today that Takeda and Arbor have entered into a license, development and commercialization agreement. It will provide Arbor 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, Arbor 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 Arbor 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 Arbor. "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 Arbor Pharmaceuticals
Arbor Pharmaceuticals Ireland Limited is a wholly-owned subsidiary of Arbor 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. Arbor currently markets multiple NDA and ANDA approved products with several more filed or in development. For more information regarding Arbor Pharmaceuticals or any of its products, visit www.arborpharma.com or send email inquiries to [email protected].

Takeda Pharmaceuticals U.S.A., Inc.
Based in Deerfield, Ill., Takeda Pharmaceuticals U.S.A., Inc. is a subsidiary of Takeda Pharmaceutical Company Limited, the largest pharmaceutical company in Japan. The respective companies currently market oral diabetes, insomnia, rheumatology, and 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.takeda.us

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 people worldwide through leading innovation in medicine. Additional information about Takeda is available through its corporate website, www.takeda.com.

This press release contains forward-looking statements. Forward-looking statements include statements regarding Takeda's plans, outlook, strategies, results for the future, and other statements that are not descriptions of historical facts. Forward-looking statements may be identified by the use of forward-looking words such as "may," "believe," "will," "expect," "project," "estimate," "should," "anticipate," "plan," "assume," "continue," "seek," "pro forma," "potential," "target," "forecast," "guidance," "outlook" or "intend" or other similar words or expressions of the negative thereof. Forward-looking statements are based on estimates and assumptions made by management that are believed to be reasonable, though they are inherently uncertain and difficult to predict. Investors are cautioned not to unduly rely on such forward-looking statements.

Forward-looking statements involve risks and uncertainties that could cause actual results or experience to differ materially from that expressed or implied by the forward-looking statements. Some of these risks and uncertainties include, but are not limited to, (1) the economic circumstances surrounding Takeda's business, including general economic conditions in Japan, the United States and worldwide; (2) competitive pressures and developments; (3) applicable laws and regulations; (4) the success or failure of product development programs; (5) actions of regulatory authorities and the timing thereof; (6) changes in exchange rates; (7) claims or concerns regarding the safety or efficacy of marketed products or product candidates in development; and (8) integration activities with acquired companies.

The forward-looking statements contained in this press release speak only as of the date of this press release, and Takeda undertakes no obligation to revise or update any forward-looking statements to reflect new information, future events or circumstances after the date of the forward-looking statement. If Takeda does update or correct one or more of these statements, investors and others should not conclude that Takeda will make additional updates or corrections.

Contacts:
Takeda Pharmaceuticals U.S.A., Inc.
Kara Hoeger
+1-224-554-1277
[email protected]

Takeda Pharmaceutical Company Limited
Corporate Communications Dept. (PR/IR)
+81-3-3278-2083

Arbor Pharmaceuticals, LLC
Brian Adams
+1-404-496-5915
[email protected]

SOURCE Takeda Pharmaceutical Company Limited