Public Release: 

First-ever published study of moderate to severe Alzheimer's disease patients taking Aricept (r) shows significant treatment benefits in cognition, daily living activities and behavior

Porter Novelli

London (28 August 2001) -- The benefits of ARICEPT® may extend into more advanced stages of Alzheimer's disease than previously investigated, according to a first-ever published study of ARICEPT® in patients with moderate to severe Alzheimer's disease.

The study, published today in Neurology (28 August 2001), found that ARICEPT® conferred significant benefits vs. placebo in patient function, cognition, behavior, and activities of daily living, with very good tolerability. In addition, improvement in all behavioral symptom items on the Neuropsychiatric Inventory (NPI) favored ARICEPT®. ARICEPT® is approved for the treatment of symptoms of mild to moderate Alzheimer's disease.

The Moderate to Severe Alzheimer's Disease Study (MSAD) is the third ARICEPT® study to be published in Neurology this month. Two additional placebo-controlled studies of patients with mild to moderate Alzheimer's disease were published in the 14 August issue: The Preservation of Function study found that 1 year of ARICEPT® treatment reduced the risk of functional decline; the Nordic study demonstrated that ARICEPT® maintained cognition, activities of daily living (ADLs), and global function for 1 year.

"These 3 research articles in Neurology represent an important convergence of information," said Howard Feldman, MD, UBC Hospital, Clinic for Alzheimer's Disease and Related Disorders, Vancouver, British Columbia. "Alzheimer's research holds promise for the future, but doctors who care for mild to moderate Alzheimer's patients and their caregivers should understand the benefits Aricept® treatment offers today and may continue to offer."

"We already know that treatment with Aricept® for people with mild to moderate Alzheimer's disease slows progression of symptoms such as cognition and loss of function, and may be associated with a delay in nursing home placement, allowing loved ones to stay at home longer," Dr. Feldman added. "The findings published today further reinforce the significance of Aricept® as an important choice to preserve patients' independence longer while they live with the disease."

No approved treatments are available for the more advanced stage of Alzheimer's disease. Further study of ARICEPT® (donepezil hydrochloride) in patients with severe Alzheimer's disease is currently under way.

ARICEPT®, the No. 1 prescribed Alzheimer's medication worldwide, is a clinically proven, well-tolerated, once-daily treatment for mild to moderate Alzheimer's disease.

MSAD Study Overview

Consistent benefits were found for ARICEPT® across the full range of measures of patient outcomes -- function, cognition, behavior, and activities of daily living -- in this 24-week, double-blind placebo-controlled trial:

Ø ARICEPT®-treated patients remained stable throughout the study on measures of function, while placebo-treated patients showed functional decline.

Ø The ARICEPT®-treated group showed less decline on average compared with placebo-treated patients on both instrumental and basic activities of daily living.

Ø The ARICEPT®-treated group showed statistically significant overall improvement vs. placebo in behavioral disturbances associated with Alzheimer's; a subanalysis of behavioral domains showed statistically significant benefits in apathy, depression, and anxiety.

These data suggest that the benefits of ARICEPT® (donepezil hydrochloride), which is indicated for mild to moderate Alzheimer's disease, may extend into the more advanced stage of Alzheimer's disease than those previously investigated, with very good tolerability. Completion rates for the study were 84% in the ARICEPT® group and 86% in placebo-treated patients. (See Table 1 for complete results and outcome measures.) The most common reason for discontinuation was adverse events (8% ARICEPT®, 6% placebo), the majority of which were rated mild in severity.

In this study, 290 patients with moderate to severe Alzheimer's disease were randomized to receive either ARICEPT® 5 mg/day for the first 28 days and 10 mg/day thereafter, based on the clinicians' judgment (n=144), or placebo (n=146). Baseline demographics were similar between the ARICEPT® and placebo groups. The study enrolled patients residing in the community or in assisted living settings but not patients requiring total nursing care. The primary efficacy measure for this study was the Clinician's Interview-Based Impression of Change With Caregiver Input (CIBIC-plus ). Seven secondary measures were also used. The average SMMSE score for patients in the study was 12 (range 5-17). Patients receiving ARICEPT® showed benefits on the CIBIC-plus, compared with those taking placebo. All other secondary measures showed significant differences between the groups in favor of ARICEPT®.

In addition to the MSAD study, the following studies were published in Neurology this month:

Preservation of Function Study of ARICEPT® (donepezil hydrochloride) in Alzheimer's Patients

This 1-year U.S. Preservation of Function study demonstrated that patients taking ARICEPT® maintained their functioning in everyday activities 72% longer, a median time of about 5 months, than those who received placebo in the study. Four hundred-fifteen patients with mild to moderate Alzheimer's disease participated in this placebo-controlled study.

1-Year Nordic Study of ARICEPT® in Patients with Mild to Moderate Alzheimer's The 1-year Nordic study demonstrated that ARICEPTâ maintained cognition, activities of daily living, and global function in mild to moderate Alzheimer's disease patients for one year compared to placebo; 286 patients with possible or probable Alzheimer's disease in 5 northern European countries -- Denmark, Finland, The Netherlands, Norway, and Sweden -- participated in the study.

Information About ARICEPT® Treatment

Alzheimer's disease, which is a progressive and degenerative brain disorder, impairs cognition and the ability to perform such daily living activities as handling money, using the telephone, grooming, etc. Approximately 15 million people suffer from AD worldwide. While there is no cure for Alzheimer's disease, medical treatments are available to manage symptoms of the disease. Once-a-day prescription ARICEPT®, indicated for mild to moderate Alzheimer's disease, can improve cognition and maintain patient function. A recent study showed that persistent treatment with ARICEPTâ may have been associated with a delay of close to 2 years (21 months) in the first dementia-related nursing home placement for Alzheimer's patients. Persistent treatment was defined in this study as an effective dose of at least 5 mg a day for at least 9 to 12 months. ARICEPTÒ is well tolerated but may not be for everyone. Some people may experience nausea, diarrhea, insomnia, vomiting, muscle cramps, fatigue or loss of appetite. In studies, these effects were usually mild and temporary. Some people taking ARICEPT® may experience fainting. People at risk for ulcers should tell their doctors because their condition may get worse.

In a progressively degenerative disease such as Alzheimer's, no further decline or a less-than-expected decline is considered a favorable response. Improvement, stabilization and decline have been observed in patients treated with ARICEPT® in clinical trials. Individual responses to treatment may vary.

ARICEPTÒ is available by prescription in more than 40 countries. In November 1994, Eisai Co., Ltd. and Pfizer Inc announced the formation of a strategic alliance for the promotion of ARICEPTÒ and development of new treatments for Alzheimer's disease and other cognitive disorders. ARICEPTÒ is the lead compound in this alliance. First launched in the United States in February 1997, ARICEPTÒ has been well-received in the Alzheimer's disease community with more than 450 million days of patient use worldwide, and more than 1.4 million people in the United States have received a prescription for ARICEPTÒ. Eisai Co., Ltd., and Pfizer Inc are committed to a collaboration dedicated to advances in Alzheimer's therapy. These studies were funded by Eisai and Pfizer Inc. Full prescribing information is available upon request from Melissa Furrie of Porter Novelli or Susan Yarin of Pfizer Inc (see contact information above).

In this trial, the common treatment-emergent adverse events occurring in ?5% and at least twice the rate of placebo-treated patients were diarrhea (12.5% vs. 4.8%), headache (11.8% vs. 4.1%), arthralgia (6.9% vs. 1.4%), and vomiting (6.9% vs. 2.7%).

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ARICEPT® is a registered trademark of Eisai Co., Ltd.
News Source: Eisai Ltd. (European Office) and Pfizer Inc.

Contact:
Melissa Furrie
Porter Novelli
+1-212-601-8232

-- Neurology, the Scientific Journal of the American Academy of Neurology, Publishes 3 ARICEPT® Studies This Month --

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