First Clinical Data for BACE Inhibitor E2609 Showcased at International Alzheimer's Conference

HATFIELD, England, July 24, 2012 /PRNewswire/ --

Eisai's new investigational molecule discovered and developed collaboratively in the UK and Japan

Eisai in Europe today releases the first clinical data for E2609, a BACE (beta-site amyloid precursor protein-cleaving enzyme) inhibitor, presented during oral sessions at the Alzheimer's Association International Conference (AAIC) 2012 in Vancouver, Canada. This novel compound was discovered through a collaborative partnership between centres in Britain, Japan and the United States (US). Eisai's European Knowledge Centre is in Hatfield, UK.

Eisai has one of the largest private dementia research groups in Britain. Through collaborative efforts with partners in the UK and colleagues in Japan, this group has been a part of key neurological discoveries including the potential new treatment for epilepsy, Fycompa® (perampanel), and now E2609.

Amyloid beta (Aβ) deposition in the brain is thought to be one of the causes of Alzheimer's disease. It is expected that developing a new treatment for Alzheimer's disease which reduces amyloid beta will not only improve symptoms, but also help slow down the progression of the disease. E2609 may reduce the overall amount of amyloid beta by inhibiting BACE.

The two E2609 Phase I studies presented at the AAIC 2012 comprised a single oral ascending dose study (SAD, Study A001-001)^[1] and a 14-day multiple oral ascending dose study (MAD, Study A001-002).^[1] The SAD study showed a reduction in plasma amyloid beta levels, whilst the MAD study showed a statistically significant reduction of cerebrospinal fluid (CSF) amyloid beta levels.^[1] Both studies showed a dose-related increase in plasma drug exposure. These Phase I study results confirm E2609 'Proof of Mechanism' for preventing amyloid beta production by BACE inhibition in humans.

"These 'First in Human' data for E2609 are encouraging as they suggest the compound has potential in treating the underlying cause of disease and slowing cognitive decline. Halting disease progression is the key area of research for dementia experts, and it is an exciting collaboration between teams in the UK, US and Japan. This Eisai developed treatment may, in the future, play a part in tackling this key area of unmet need," said researcher Dr Robert Lai, Senior Director, Neuroscience Product Creation Unit (PCU) at Eisai's European Knowledge Centre.

Study A001-001 was a randomised, double-blind, placebo-controlled, single ascending dose study conducted in 73 healthy adult volunteers. Subjects were divided into nine cohorts to receive E2609 doses of between 5 mg to 800 mg. Plasma amyloid beta [amyloid Beta(1-x)] levels were measured prior to patients receiving E2609 and then at multiple time points up to 144 hours post-dose. The maximum dose-dependent reduction of plasma amyloid beta (1-X) relative to baseline was 52% at 5 mg, and 92% at 800 mg. E2609 showed acceptable tolerability across all doses, and the most common adverse events included headache and dizziness.^[1]

Study A001-002 was a randomised, double-blind, placebo-controlled, multiple ascending dose study conducted in 50 healthy adult volunteers. Subjects were divided into five cohorts, with each cohort receiving E2609 doses of between 25 mg and 400 mg per day for 14 days. The study measured amyloid beta levels both in plasma and CSF. Preliminary interim analysis results showed that E2609 demonstrated a clear reduction in plasma amyloid beta (1-X) levels and a dose-dependent reduction in CSF amyloid Beta(1-X) in subjects who received daily doses of between 25 mg and 200 mg. The percentage decrease in CSF amyloid Beta(1-x) after 14 days dosing compared to baseline was statistically significant, with E2609 demonstrating a 46.2%, 61.9%, 73.8% and 79.9% difference in percentage decrease compared to placebo in the 25 mg, 50 mg, 100 mg and 200 mg cohorts, respectively. No clinically significant safety concerns were observed following repeated oral dosing of up to 200 mg. Several cases of orolabial herpes relapse were observed in the 200 mg cohort, however, while being evaluated, the significance of these cases is unknown as the blind remains unbroken on the safety data.^[1]

Alzheimer's disease remains an area with a large number of unmet medical needs and the discovery and development of E2609 underscores Eisai's human health care mission, the company's commitment to innovative solutions in disease prevention, cure and care for the health and well-being of people worldwide. Aiming to develop next-generation Alzheimer's disease treatments, Eisai is also pursuing the development of the novel monoclonal antibody BAN2401 targeting amyloid beta protofibrils, and other compounds in addition to E2609, as it seeks to make further contributions to address the diversified needs of, and increase the benefits provided to, Alzheimer's disease patients and their families.

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.^[2] There were an estimated 7.2 million people in the EU living with dementia in 2008, costing the region's economy an estimated €160 billion per year, of which 55% is informal care provided by family members, friends or volunteers.^[3]

About Eisai in Alzheimer's disease

Since launching the Alzheimer's disease treatment Aricept^®, Eisai has been committed to enhancing the value that the drug provides patients through the development of new formulation types carrying out disease awareness-raising activities aimed at promoting early diagnosis and treatment, and the improvement of diagnostic technologies. In addition, Eisai is pursuing the development of novel compounds to make further contributions to address the diversified needs of, and increase the benefits provided to, Alzheimer's disease patients and their families.

About Eisai

Eisai is one of the world's leading R&D-based pharmaceutical companies and 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 recently expanded their UK Hatfield facility which now supports the company's growing European, Middle Eastern, African and Russian (EMEA) business.

Eisai concentrates its R&D activities in three key areas:

• Neuroscience, including: Alzheimer's disease, multiple sclerosis, neuropathic pain, epilepsy, depression
• Oncology including: anticancer therapies; tumour regression, tumour suppression, antibodies, etc and supportive cancer therapies; pain relief, nausea
• Vascular/Immunological reaction including: acute coronary syndrome, atherothrombotic disease, rheumatoid arthritis, psoriasis, Crohn's disease

With operations in the U.S., Asia, Europe and its domestic home market of Japan, Eisai employs more than 11,000 people worldwide. 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, Slovakia, the Netherlands, Belgium, Luxembourg, the Middle East and Russia.

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

References

1. Eisai Data on File

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

3. 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: http://www.alzheimer-europe.org/Our-Research/European-Collaboration-on-Dementia/Cost-of-dementia/Cost-of-illness-and-burden-of-dementia. Last accessed July 2012

Date of preparation: July 2012

Job code: Corporate-UK2005