New Data Demonstrate Efficacy and Tolerabilty of Bystolic(R) (Nebivolol) Tablets among Hispanics with Hypertension

NEW YORK, May 03, 2010 (BUSINESS WIRE) --Forest Laboratories, Inc. (NYSE: FRX) today presented data from a Phase IV study evaluating the effects of Bystolic(R) (nebivolol) tablets in Hispanic patients with hypertension at the 2010 annual scientific meeting of the American Society of Hypertension (ASH). Results showed Bystolic significantly reduced sitting systolic (p=0.001) and diastolic (p<0.0001) blood pressure (BP) when used as monotherapy and was well tolerated. Bystolic is a beta blocker approved by the U.S. Food and Drug Administration for the treatment of mild to moderate hypertension and can be used alone or in combination with other antihypertensive treatments.

Hispanics currently comprise 14% of the total U.S. population and are the fastest growing minority group in the U.S. By 2050, this number is expected to increase by 25%. A study by the National Center for Health Statistics found over 20% of adult Hispanics have hypertension, which can eventually lead to heart attack, stroke and kidney failure. Hispanics also have higher rates of diabetes and obesity, compared with Caucasians, additional risk factors for developing hypertension. Data from the National Health and Nutrition Examination Survey (NHANES) show Mexican Americans, who comprise the majority of Hispanics in the U.S., tend to have lower awareness of their hypertension, are less likely to be treated with medication for the condition, and have lower blood pressure control, compared with African Americans and Caucasians.

"Bystolic is one of the only antihypertensives to have been prospectively evaluated for efficacy and safety in Hispanic patients, which is important given the lack of awareness, poor control, and risk factors in this growing population," explains Henry Punzi, MD, Clinical Assistant Professor, Department of Family and Community Medicine, University of Texas Southwestern Medical Center in Dallas, TX, and study investigator. "These positive results show Bystolic is an effective treatment option with good tolerability for Hispanic patients with hypertension and add to the growing body of evidence in support of the clinical profile of the drug."

About the Study

The study was an eight-week randomized, double-blind, placebo-controlled, dose-titration trial that was conducted in multiple centers in the U.S. to evaluate the efficacy and safety of Bystolic in Hispanic patients with Stage I and II hypertension. Participants included 113 female and 164 male Hispanic patients 18 years and older with Stage I-II hypertension (sitting diastolic BP greater-than or equal to 95 mm Hg and less-than or equal to 114 mm Hg). Patients were randomized to receive either Bystolic (5 mg) (n=141) or placebo (n=136) and dose was titrated at 2-week intervals in patients who did not achieve BP control, to a maximum dose of 40 mg.

Patients treated with Bystolic achieved double digit blood pressure reductions in both systolic (p=0.001) and diastolic (p<0.0001) blood pressure. At week 8, mean change from baseline was -14.1/-11.1 mm Hg for Bystolic versus -9.3/-7.3 mm Hg for placebo patients. The overall incidence of treatment-emergent adverse events was similar in the placebo (24.3%) and Bystolic (23.4%) groups. The discontinuation rate due to adverse events was 0% for Bystolic compared to 4.4% for placebo. The most frequently observed adverse events were headache, upper respiratory tract infection, and dizziness, and occurred in Bystolic patients at rates equal to or less than that observed in placebo-treated patients.

Additional Data Presented Demonstrates Persistence of Antihypertensive Effect of Bystolic

Forest Laboratories also presented positive results from a Phase IV multicenter study evaluating the persistence of the antihypertensive effect of nebivolol following medication withdrawal. Results showed Bystolic reduced sitting systolic and diastolic BP over an initial 12-week single-blind treatment phase. The antihypertensive response to Bystolic was maintained in a subsequent four-week double-blind phase of the study in which patients were randomized to remain on a stable dose of Bystolic or be switched to placebo. In comparison, patients who were switched to placebo demonstrated a gradual increase in BP, with a mean difference between Bystolic and placebo of 4.1 mm Hg for systolic BP (p=0.01) and 5.7 mm Hg (p<0.0001) for diastolic BP. The most frequent AEs during the 12-week single-blind open-label treatment phase were bradycardia, nasopharyngitis, and headache, each occurring at rates <6%. During the 4-week double-blind phase, adverse events were infrequent and comparable between Bystolic and placebo patients, and caused no study discontinuations.

About Hypertension

Hypertension, also known as high blood pressure, affects more than 74 million people in the U.S. and nearly 56 percent of patients diagnosed with hypertension have not reduced their blood pressure to an acceptable range (less-than or equal to 140/90 mm Hg for most patients). Hypertension is a major risk factor for heart disease, the leading cause of death in the United States. Hypertension is dangerous because it makes the heart work harder and contributes to atherosclerosis (hardening of the arteries), which can lead to angina (chest pain or damage to the heart muscle) or to heart attack. If left untreated, hypertension can eventually damage important organs such as the heart, brain, eyes or kidneys. People with untreated hypertension are much more likely to die or be disabled by cardiovascular complications than those with normal blood pressure.

About Bystolic

Bystolic (nebivolol) was approved by the U.S. Food and Drug Administration in 2007 for the treatment of hypertension (chronic high blood pressure). Bystolic is a once-daily medication effective at lowering blood pressure when taken alone or in combination with other high blood pressure medications. The mechanism of action of the antihypertensive response of Bystolic has not been definitively established. Like other beta blockers, possible factors that may be involved include decreased heart rate and myocardial contractility, and suppression of renin activity. Bystolic is a selective beta 1 blocker at doses less than or equal to 10 mg per day and has the added pharmacological properties of producing vasodilation and reducing total peripheral resistance. It is available in 2.5 mg, 5 mg, 10 mg and 20 mg tablets. In clinical trials, the discontinuation rate due to adverse events was 2.8% for Bystolic versus 2.2% for placebo. Nebivolol is approved and marketed in 60 countries outside of North America.

Important Safety Information

Contraindications

• BYSTOLIC is contraindicated in patients with severe bradycardia, heart block greater than first degree, cardiogenic shock, decompensated cardiac failure, sick sinus syndrome (unless a permanent pacemaker is in place), severe hepatic impairment (Child-Pugh >B), and in patients who are hypersensitive to any component of this product.

Warnings and Precautions

• Do not abruptly discontinue BYSTOLIC therapy in patients with coronary artery disease. Severe exacerbation of angina, myocardial infarction, and ventricular arrhythmias have been reported following the abrupt discontinuation of therapy with beta blockers. Myocardial infarction and ventricular arrhythmias may occur with or without preceding exacerbation of the angina pectoris. Caution patients without overt coronary artery disease against interruption or abrupt discontinuation of therapy.
• As with other beta blockers, when discontinuation of BYSTOLIC is planned, carefully observe and advise patients to minimize physical activity. Taper BYSTOLIC over 1 to 2 weeks when possible. If the angina worsens or acute coronary insufficiency develops, restart BYSTOLIC promptly, at least temporarily.
• BYSTOLIC was not studied in patients with angina pectoris or who had a recent MI.
• In general, patients with bronchospastic diseases should not receive beta blockers.
• Because beta blocker withdrawal has been associated with an increased risk of MI and chest pain, patients already on beta blockers should generally continue treatment throughout the perioperative period. If BYSTOLIC is to be continued perioperatively, monitor patients closely when anesthetic agents which depress myocardial function, such as ether, cyclopropane, and trichloroethylene are used. If beta-blocking therapy is withdrawn prior to major surgery, the impaired ability of the heart to respond to reflex adrenergic stimuli may augment the risks of general anesthesia and surgical procedures.
  
  The beta-blocking effects of BYSTOLIC can be reversed by beta agonists, eg, dobutamine or isoproterenol. However, such patients may be subject to protracted severe hypotension. Additionally, difficulty in restarting and maintaining the heartbeat has been reported with beta blockers.
• Beta blockers may mask some of the manifestations of hypoglycemia, particularly tachycardia. Advise patients subject to spontaneous hypoglycemia and diabetic patients receiving insulin or oral hypoglycemic agents about these possibilities.
• Beta blockers may mask clinical signs of hyperthyroidism, such as tachycardia. Abrupt withdrawal of beta blockers in these patients may be followed by an exacerbation of symptoms or may precipitate a thyroid storm.
• Beta blockers can precipitate or aggravate symptoms of arterial insufficiency in patients with peripheral vascular disease.
• Because of significant negative inotropic and chronotropic effects in patients treated with beta blockers and calcium channel blockers of the verapamil and dilitiazem type, monitor the ECG and blood pressure of patients treated concomitantly with these agents.
• Use caution when BYSTOLIC is co-administered with CYP2D6 inhibitors (quinidine, propafenone, fluoxetine, paroxetine, etc). When BYSTOLIC is co-administered with an inhibitor or an inducer of CYP2D6, monitor patients closely and adjust the nebivolol dose according to blood pressure response. The dose of BYSTOLIC may need to be reduced. When BYSTOLIC is administered with fluoxetine, significant increases in d-nebivolol may be observed (ie, an 8-fold increase in AUC and a 3-fold increase in C_max for d-nebivolol).
• Renal clearance of nebivolol is decreased in patients with severe renal impairment. In patients with severe renal impairment (ClCr less than 30 mL/min) the recommended initial dose is 2.5 mg once daily; titrate up slowly if needed. BYSTOLIC has not been studied in patients receiving dialysis.
• Metabolism of nebivolol is decreased in patients with moderate hepatic impairment. In patients with moderate hepatic impairment, the recommended initial dose is 2.5 mg once daily; titrate up slowly if needed. BYSTOLIC has not been studied in patients with severe hepatic impairment and therefore it is not recommended in that population.
• Patients with a history of severe anaphylactic reactions to a variety of allergens may be more reactive to repeated challenge and may be unresponsive to the usual doses of epinephrine while taking beta blockers.
• In patients with known or suspected pheochromocytoma, initiate an alpha blocker prior to the use of any beta blocker.

Drug Interactions

• Do not use BYSTOLIC with other beta blockers.
• Both digitalis glycosides and beta blockers slow atrioventricular conduction and decrease heart rate. Concomitant use can increase the risk of bradycardia.
• BYSTOLIC can exacerbate the effects of myocardial depressants or inhibitors of AV conduction, such as certain calcium antagonists (particularly of the phenylalkylamine [verapamil] and benzothiazepine [diltiazem] classes), or antiarrhythmic agents, such as disopyramide.

Use in Specific Populations

• Use BYSTOLIC during pregnancy only if the potential benefit justifies the potential risk to the fetus. BYSTOLIC is not recommended during nursing.
• The safety and effectiveness of BYSTOLIC have not been established in pediatric patients.
• In a placebo-controlled trial of 2128 patients (1067 BYSTOLIC, 1061 placebo) over 70 years of age with chronic heart failure receiving a maximum dose of 10 mg per day for a median of 20 months, no worsening of heart failure was reported with nebivolol compared to placebo. However, if heart failure worsens, consider discontinuation of BYSTOLIC.

Adverse Reactions

• The most common adverse events with BYSTOLIC versus placebo (approximately greater-than or equal to 1% and greater than placebo) were headache, fatigue, dizziness, diarrhea, nausea, insomnia, chest pain, bradycardia, dyspnea, rash, and peripheral edema. The most common adverse events that led to discontinuation of BYSTOLIC were headache (0.4%), nausea (0.2%), and bradycardia (0.2%).

About Forest Laboratories

Forest Laboratories (NYSE: FRX) is a U.S.-based pharmaceutical company with a long track record of building partnerships and developing and marketing products that make a positive difference in people's lives. In addition to its well-established franchises in therapeutic areas of the central nervous and cardiovascular systems, Forest's current pipeline includes product candidates in all stages of development and across a wide range of therapeutic areas. The Company is headquartered in New York, NY. To learn more about Forest Laboratories, visit http://www.FRX.com.

Except for the historical information contained herein, this release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. These statements involve a number of risks and uncertainties, including the difficulty of predicting FDA approvals, the acceptance and demand for new pharmaceutical products, the impact of competitive products and pricing, the timely development and launch of new products, and the risk factors listed from time to time in Forest Laboratories' Annual Report on Form 10-K, Quarterly Reports on Form 10-Q, and any subsequent SEC filings.

SOURCE: Forest Laboratories, Inc.

Forest Laboratories, Inc.
Frank J. Murdolo, Vice President-Investor Relations
212-224-6714
Frank.Murdolo@frx.com