FDA Advisory Committee Recommends Against Approval of Actavis' Nebivolol/Valsartan Fixed-Dose Combination NDA for Treatment of Hypertension

DUBLIN, Sept. 9, 2014 /PRNewswire/ -- Actavis plc (NYSE: ACT) today confirmed that the U.S. Food and Drug Administration's (FDA) Cardiovascular and Renal Drugs Advisory Committee (CRDAC) has voted to recommend against approval of Actavis' New Drug Application (NDA) for the fixed-dose combination of nebivolol and valsartan for the treatment of hypertension.  The committee vote was six to four recommending against approval.

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The committee recommendation is not binding on the FDA, which makes the final decision regarding approval.  Actavis expects FDA action on its NDA for the fixed-dose combination of nebivolol and valsartan by the fourth quarter of 2014.

"Although we are disappointed in the Committee's recommendation regarding the fixed-dose combination of nebivolol and valsartan, we remain fully committed to supporting the NDA for this important potential new treatment option for patients with hypertension," said David Nicholson, Senior Vice President, Global Brands Research and Development, Actavis. "We remain confident in the safety and efficacy of the combination of these two widely used and well-tolerated treatments, and we look forward to working with the FDA as it completes its review."

Data presented at today's Advisory Committee meeting included phase III efficacy and safety data from the almost 5,000-patient nebivolol/valsartan clinical development program. In the pivotal efficacy study published in The Lancet, the fixed-dose combination (FDC) of nebivolol and valsartan met its primary and key secondary endpoints, demonstrating statistically significant reductions from baseline in diastolic and systolic blood pressure at eight weeks in patients with hypertension versus both nebivolol alone and valsartan alone. The adverse event profile of the fixed dose combination was similar to that observed with the monotherapies and placebo. In addition, a 52-week open-label safety study further supported the favorable long-term safety profile of the nebivolol/valsartan combination.

About Nebivolol and Valsartan

Nebivolol/valsartan (5/80mg, 5/160mg, 10/160mg, 10/320mg, and 20/320mg) is an investigational fixed-dose combination. It combines two FDA approved, once daily, blood pressure lowering agents with different mechanisms of action. It is being evaluated as a potential treatment for hypertension in patients who need combination therapy.

Nebivolol (marketed in the U.S. as Bystolic) is indicated for the treatment of hypertension and is effective at lowering blood pressure when taken alone or in combination with other antihypertensive agents such as ACEIs, ARBs, and/or diuretics. It is Beta-1 selective up to and including the 10mg dose and in extensive metabolizers. While nebivolol's mechanism of action has not been definitively established, possible factors include vasodilation and decreased peripheral vascular resistance (PVR), reduced heart rate and myocardial contractility, suppression of renin, and reduced sympathetic activity.

Valsartan has been well studied in many different patient populations and is an effective antihypertensive agent. It is an angiotensin II receptor blocker (ARB) that blocks the binding of angiotensin II to the AT1 receptor in many tissues, such as vascular smooth muscle and the adrenal gland, thereby preventing its vasoconstrictor and aldosterone-secreting effects.

About Hypertension

According to the CDC, hypertension has been called the "silent killer" because it often has no warning signs or symptoms and has been associated with serious cardiovascular (CV) risks, such as stroke and myocardial infarction. Hypertension represents a significant public health issue with high prevalence. According to the National Institute for Health Statistics, approximately 30 percent of adults in the United States have hypertension. Inadequate control of hypertension is a significant public health problem, with more than half of all patients still not achieving target goals. Numerous antihypertensive drugs, from a variety of pharmacologic classes and with different mechanisms of action, have been shown in randomized controlled trials to reduce CV morbidity and mortality, and it can be concluded that it is BP reduction that is largely responsible for those benefits. Two-thirds of hypertensive patients will require more than one drug to achieve blood pressure goals.

About Actavis

Actavis plc (NYSE: ACT), headquartered in Dublin, Ireland, is a unique specialty pharmaceutical company focused on developing, manufacturing and commercializing high quality affordable generic and innovative branded pharmaceutical products for patients around the world. 

Actavis markets a broad portfolio of branded and generic pharmaceuticals and develops innovative medicines for patients suffering from diseases principally in the central nervous system, gastroenterology, women's health, urology, cardiovascular, respiratory and anti-infective therapeutic categories.  The Company is an industry leader in product research and development, with one of the broadest brand development pipelines in the pharmaceutical industry, and a leading position in the submission of generic product applications.  Actavis has commercial operations in more than 60 countries and operates more than 30 manufacturing and distribution facilities around the world.

For more information, visit Actavis' website at www.actavis.com.

Forward-Looking Statement

Statements contained in this press release that refer to future events or other non-historical facts are forward-looking statements that reflect Actavis' current perspective of existing trends and information as of the date of this release.  Actual results may differ materially from Actavis' current expectations depending upon a number of factors affecting Actavis' business. These factors include, among others, the difficulty of predicting the timing or outcome of FDA approvals or actions, if any; the impact of competitive products and pricing; market acceptance of and continued demand for Actavis' products; difficulties or delays in manufacturing; and other risks and uncertainties detailed in Actavis' periodic public filings with the Securities and Exchange Commission, including but not limited to Actavis plc's Annual Report on Form 10-K for the year ended December 31, 2013, Quarterly Report on Form 10-Q for the quarter ended June 30, 2014 and from time to time in Actavis' other investor communications. Except as expressly required by law, Actavis disclaims any intent or obligation to update or revise these forward-looking statements.

CONTACTS: Investors:

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Media:
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SOURCE Actavis plc