New Study Shows Evidence of Lower Rate of Hippocampal Shrinkage in Alzheimer’s Disease Patients Treated With Aricept(R)

LONDON, July 20, 2011 /PRNewswire/ --

Eisai Europe Ltd and Pfizer Limited today announced the results from a new study conducted in France demonstrating Aricept® (donepezil hydrochloride) 10mg significantly reduced the rate of hippocampal atrophy (reduction in volume) in patients with an amnestic syndrome at an early phase of Alzheimer's disease.

The multi-centre, double-blind, randomised, placebo-controlled study was conducted to assess the effect of donepezil on the rate of hippocampal atrophy over one year in patients presenting an amnestic syndrome at a mild cognitive impairment (MCI) stage of the disease.  A total of 216 patients were randomised to receive donepezil 10 mg daily or placebo.^[1] The study was conducted outside the licensed indication for donepezil in the European Union. Aricept is licensed for the symptomatic treatment of mild to moderately severe Alzheimer's dementia in Europe.

The adverse events reported were consistent with the known safety profile of donepezil.^[2] The most commonly reported adverse events in this study were headaches, nightmares, cramps, nausea and diarrhea.

Patients in the donepezil group exhibited a 45% lower rate of hippocampal atrophy than those in the placebo group after 1 year (-1.89% [SE=0.34] vs -3.74% [SE=0.32], p<0.001). There was no difference between the donepezil and placebo groups on any of the cognitive measures included in the study*. The full results of the study will be presented at the Alzheimer's Association International Conference 2011 (AAIC 2011) in Paris, France.

The hippocampus plays an important role in short-term and long-term memory and spatial navigation.^[3] In Alzheimer's disease, the hippocampus is one of the first regions of the brain to suffer damage, with symptoms often presenting as memory problems and disorientation. Hippocampal atrophy has been identified as a common feature in Alzheimer's disease, and shrinkage in the hippocampal region has been shown to correlate with severity of the patient's decline.^[4]

Commenting on this new study, Professor Bruno Dubois from the Neurological Institute of the Salpétrière University Hospital in Paris who led the study said: “These findings are important as the results show that subjects on donepezil 10mg displayed significantly less hippocampal atrophy after one year compared to subjects receiving placebo. This study also used the new diagnostic framework recently proposed by the International Working Group for New Research and Criteria for Diagnosis of Alzheimer's disease.^[5]”

The hippocampus study is a result of a collaboration between the top centres in France, including Hôpital de la Pitié Salpêtriere.

Notes to Editors

*Cognitive measures for the study included:

• Mean change in the sum of items of the Alzheimer's Disease Assessment Scale - Cognitive - Mild Cognitive Impairment version (ADAS-Cog-MCI) from Baseline to 12 month visit
• Mean change from Baseline to Endpoint in the sum of items of the MMSE from Baseline to 12 month visit
• Mean change of Modified Isaacs test score from Baseline to Endpoint
• Mean change of California Verbal Learning Test score from Baseline to 12 month visit
• Mean change of time to perform the Trail Making Test A and B and number of errors from Baseline to 12 month visit
• Mean change of Benton Visual Retention scorefrom Baseline to 12 month visit
• Mean change of McNair scorefrom Baseline to 12 month visit

About Aricept® (donepezil)

Aricept is an acetylcholinesterase inhibitor (AChEI) licensed in the European Union for the symptomatic treatment of mild to moderately severe Alzheimer's dementia.

About mild cognitive impairment^[6]

Mild cognitive impairment represents an intermediate state of cognitive function between the changes seen in aging and those fulfilling the criteria for dementia and often Alzheimer's disease.

About Alzheimer's disease

Alzheimer's disease is the most common form of dementia. This irreversible, progressive brain disorder gradually destroys memory, reasoning and thinking skills, and may eventually leave patients unable to carry out even the simplest tasks.^[7]  Dementia currently 5.4 million people in the EU, and is estimated to cost the EU economy €160 billion per year, of which 55% is informal care provided by family members, friends or volunteers.^[8]

About Eisai

Eisai is one of the world's leading Research & Development-based pharmaceutical companies that has defined its corporate mission as “giving first thought to patients and their families and to increasing the benefits health care provides,” which we call human health care (hhc).

Eisai concentrates its Research & Development activities in three key areas:

• Neuroscience: Alzheimer's disease, multiple sclerosis, neuropathic pain, epilepsy, depression
• Oncology: Anticancer therapies; tumour regression, tumour suppression, antibodies, and supportive cancer therapies; pain relief, nausea
• Vascular/Immunological Reaction: Acute coronary syndrome, atherothrombotic disease, sepsis, rheumatoid arthritis, psoriasis, Crohn'’s disease

With operations in the U.S., Asia, Europe and its domestic home market of Japan, we employ more than 10,000 people worldwide, and reported consolidated sales of over £3.53 billion in FY2007, an increase of 8.9% year on year. In Europe, Eisai undertakes sales and marketing operations in over 20 markets, including the United Kingdom, France, Germany, Italy, Spain, Switzerland, Sweden, Ireland, Austria, Denmark, Finland, Norway, Portugal, Iceland, Czech Republic, Hungary, Slovakia and the Netherlands.

For further information please visit our web site http://www.eisai.com

About Pfizer: Working Together for a Healthier World™

At Pfizer, we apply science and our global resources to improve health and well-being at every stage of life. We strive to set the standard for quality, safety and value in the discovery, development and manufacturing of medicines for people and animals. Our diversified global health care portfolio includes human and animal biologic and small molecule medicines and vaccines, as well as nutritional products and many of the world'’s best-known consumer products. Every day, Pfizer colleagues work to advance wellness, prevention, treatments and cures that challenge the most feared diseases of our time. Consistent with our responsibility as the world's leading biopharmaceutical company, we also collaborate with health care providers, governments and local communities to support and expand access to reliable, affordable health care around the world. For more than 150 years, Pfizer has worked to make a difference for all who rely on us.

For further information please visit our web site: http://www.pfizer.com

References:

1. Eisai Data on File (ICAD Abstract Presentation)

2. Aricept SPC: Available from http://www.medicines.org.uk/emc/medicine/577/SPC/ (Last updated 27 July 2010)

3. Burgess, N. The hippocampus, space, and viewpoints in episodic memory. The Quarterly Journal of Experimental Psychology 2002, 55A (4), 1057 - 1080

4. Yavuz BB, Ariogul S, Cankurtaran M, Oguz KK, Halil M, Dagli N, Cankurtaran ES. Hippocampal atrophy correlates with the severity of cognitive decline. Int Psychogeriatr 2007 19 (4): 767 -77

5. Dubois, B. et al. Revising the definition of Alzheimer'’s disease: a new lexicon. The Lancet Neurology (2010), (9) 1118 -– 1127

6. Petersen, R. Mild cognitive impairment. NEJM (2011) 364: 2227 -– 2234

7. National Institute on Aging (NIA). Alzheimer'’s Disease Factsheet. NIH Publication No 08-6423. Reprinted February 2010

8. Alzheimer Europe: European Collaboration on Dementia: Cost of illness and burden of dementia: Anders Wimo, Karolinska Institutet, Linus Jönsson, I3 Innovus and Anders Gustavsson, Senior Analyst, I3 Innovus. Available at URL: http://www.alzheimer-europe.org/Our-Research/European-Collaboration-on-Dementia/Cost-of-dementia/Cost-of-illness-and-burden-of-dementia Last accessed July 2011