Namenda(TM) (memantine HCl) Provides Functional and Behavioral Benefits in Patients with Moderate to Severe Alzheimer's Disease

NEW YORK, May 6, 2004 /PRNewswire-FirstCall via COMTEX/ -- Forest Laboratories, Inc. (NYSE: FRX) announced today the presentation of functional and behavioral outcomes data from the first Phase III, randomized, placebo-controlled, clinical trial to examine the treatment of patients with moderate to severe Alzheimer's disease with a combination of two available Alzheimer's drugs. The study results, previously presented, demonstrate that patients treated with Namenda(TM) (memantine HCl) and a stable dose of donepezil maintain significantly higher functional abilities, such as grooming and toileting, and exhibit improved behavioral symptoms, including irritability and agitation, when compared to patients receiving donepezil and placebo. The analysis of behavioral and functional data presented today at the American Psychiatric Association (APA) annual meeting in New York is based on the results of a study recently reported in the Journal of the American Medical Association.

"The loss of ability to perform tasks such as dressing or bathing oneself and the behavioral disturbances associated with Alzheimer's disease, can lead to the loss of autonomy, increased need for care, and frequently lead to nursing home placement," said study lead investigator Pierre Tariot, M.D., Professor of Psychiatry, Medicine, and Neurology at the University of Rochester.

Namenda Shown to Maintain Daily Function and Reduce Behavioral Disturbances

The data, drawn from 404 patients, showed that Alzheimer's patients treated with Namenda and donepezil demonstrated significantly higher functional ability as measured by the Alzheimer's Disease Cooperative Study -- Activities of Daily Living (ADCS-ADL19), p=0.028, compared to patients treated with donepezil alone. The ADCS-ADL19 is a measurement scale that assesses patients' capabilities across 19 activities of daily living, including activities necessary for personal care, communicating and interacting with others, performing simple domestic chores, maintaining autonomy, making judgments and decisions. Patients treated with Namenda and donepezil showed statistically significant benefits compared to donepezil alone based on several activities including grooming (p=0.004), being left alone (p=0.033), and toileting (p=0.05).

Patients receiving Namenda and donepezil also experienced an overall reduction in behavioral disturbances and psychiatric symptoms relative to baseline, while patients treated with donepezil alone experienced an increase or worsening of these symptoms. The frequency and severity of behavioral disturbances were evaluated in aggregate by the Neuropsychiatric Inventory (NPI), a standard assessment scale that measures a range of common behavioral symptoms often associated with Alzheimer's disease. The difference between the two groups in the change from baseline at the six-month endpoint on the NPI in this trial was statistically significant (p=0.002). Several individual behaviors that showed statistically significant improvement included: agitation/aggression (p=0.001), irritability/lability (p=0.005), and appetite/eating change (p=0.045).

In general, the incidence of treatment-emergent adverse events was similar in patients treated with Namenda/donepezil and placebo/donepezil. A significantly greater percentage of patients in the Namenda/donepezil group (85 percent vs. 75 percent) completed the study compared to the placebo/donepezil group (p=0.01).

These results expand upon the data from this landmark combination study published earlier this year in The Journal of the American Medical Association (Vol 291, No. 3) that demonstrated that patients with moderate to severe Alzheimer's disease taking a combination of Namenda and donepezil experienced significant cognitive, functional, and global benefits compared to patients treated with donepezil alone.

Study Design

The six-month study included 404 patients at 37 sites and was a double-blind, placebo-controlled, Phase III trial. Study patients were required to have been receiving a stable dose of donepezil for at least three months prior to entry, and all patients were to have been treated with donepezil for a minimum of six months prior to entry. Patients were then randomized to receive 10 mg of Namenda twice a day, or placebo.

Behavioral Disturbances and Daily Functioning for the Alzheimer's Patient

The neurological damage caused by Alzheimer's disease can lead to difficulty performing familiar tasks. Patients lose the ability to perform everyday activities such as dressing, eating, grooming, bathing, and toileting. People with Alzheimer's disease may not be able to perform these types of functions without varying levels of assistance, and people with severe disease may not be able to perform them at all.

Alzheimer's disease can also cause a person to exhibit marked behavioral changes that are difficult for caregivers to manage. These symptoms can include withdrawal, apathy, depression, hostility, anger, and aggression, with most patients exhibiting some or all of these symptoms during the course of the disease. As the disease progresses, behavioral symptoms often increase in frequency and severity. Managing a patient's behavioral symptoms is an important component of treatment regimens for Alzheimer's disease.

About Namenda

Namenda (memantine HCl) is the first in a new class of medications with a unique mechanism of action that focuses on the glutamate pathway, a new target for the treatment of Alzheimer's disease. Indicated for the treatment of moderate to severe Alzheimer's disease, Namenda was recently approved by the FDA based on the results of three placebo-controlled studies which demonstrated Namenda's efficacy as monotherapy, or when used in combination. Results from the two U.S. studies in moderate to severe Alzheimer's disease have been published in The New England Journal of Medicine and The Journal of the American Medical Association.

Namenda (memantine HCl) is contraindicated in patients with known hypersensitivity to memantine HCl or any excipients used in the formulation. The most common adverse events reported with Namenda vs placebo (less than or equal to 5% and higher than placebo) were dizziness, confusion, headache, and constipation. In patients with severe renal impairment the use of Namenda has not been systematically evaluated and is not recommended.

About Forest Laboratories and Its Products

Forest Laboratories growing line of products includes: Namenda(TM), an N-methyl-D-aspartate (NMDA)-receptor antagonist indicated for the treatment of moderate to severe Alzheimer's disease; Lexapro(TM), an SSRI antidepressant indicated for the initial and maintenance treatment of major depressive disorder and for generalized anxiety disorder; Celexa(TM), an antidepressant; Tiazac(R), a once-daily diltiazem, indicated for the treatment of angina and hypertension; Benicar(R)*, an angiotensin receptor blocker indicated for the treatment of hypertension; Benicar HCT(TM), an angiotensin receptor blocker and diuretic combination product indicated for the second-line treatment of hypertension; and Aerobid(R), an inhaled steroid indicated for the treatment of asthma.

Forest Laboratories markets Namenda(TM) (memantine HCl) in the United States under license from Merz Pharma GmbH & Co. KGaA of Germany. Lundbeck, under license from Merz, markets memantine as Ebixa(R)*, and Merz markets memantine as Axura(R)*, each in a number of worldwide markets.

* Benicar(R) is a registered trademark of Sankyo Pharma, Inc., Ebixa(R) is a registered trademark of H. Lundbeck A/S and Axura(R) is a registered trademark of Merz Pharma GmbH & Co. KGaA.

Except for historical information contained herein, this release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995. These statements are subject to risks and uncertainties that affect our business, including risk factors listed from time to time in the Company's SEC reports, including the Company's Annual Report on Form 10-K for the fiscal year ended March 31, 2003, and Quarterly Reports on Form 10-Q for the periods ending June 30, 2003, September 30, 2003, and December 31, 2003. Actual results may differ materially from those projected.

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