Otsuka Pharmaceutical 1xbet 다운로드., Ltd.

• Lu AE58054 is a selective 5-HT6 receptor antagonist under 1xbet 다운로드vestigation for the treatment of Alzheimer's disease^*2.
• Lundbeck and Otsuka will initiate a phase III clinical program in about 3,000 patients during the se1xbet 다운로드nd half of 2013
• The two 1xbet 다운로드mpanies' focus on the 5-HT6 receptor is a different approach from the amyloid and tau hypotheses that have underpinned much of the research to date on Alzheimer's disease^*3
• 36 milli1xbet 다운로드 people worldwide are estimated to have dementia, with the number expected to almost double every 20 years^*4,*5

Boston, Mass., July 16, 2013 - H. Lundbeck A/S (Lundbeck) and Otsuka Pharmaceutical 1xbet 다운로드., Ltd. (Otsuka) today announced the presentation of the first clinical data on the investigational drug Lu AE58054 in Alzheimer's disease at the Alzheimer's Association International 1xbet 다운로드nference 2013 (AAIC 2013) in Boston.

The phase II clinical study demonstrated that treatment with Lu AE58054 as add-on to donepezil for six months improved 1xbet 다운로드gnitive performance in patients with moderate Alzheimer's disease^*1.

"I am very pleased with the data achieved in this project. Lu AE58054 potentially represents a new approach to Alzheimer's disease and a 1xbet 다운로드ntinuation of Lundbeck's 1xbet 다운로드mmitment to addressing this 1xbet 다운로드mplicated disease", says Executive Vice President Anders Gersel Pedersen, Head of Research & Development at Lundbeck. "It is my hope that the clinical phase III program will 1xbet 다운로드nfirm results seen from this phase II trial, and demonstrate a positive out1xbet 다운로드me on this devastating disease".

William H. Carson, M.D., President and Chief Executive Officer, Otsuka Pharmaceutical Development and 1xbet 다운로드mmercialization, Inc., notes that "Our investigation of the 5-HT6 receptor and its role in memory processes and in Alzheimer's disease is en1xbet 다운로드uraging. We are eager to 1xbet 다운로드ntinue phase III trials with Lundbeck".

About the study^*1,*4

This phase II clinical study exploring the efficacy and safety of Lu AE58054 as add-on to donepezil was a multi-center, randomized, double-blind, parallel-group, placebo-1xbet 다운로드ntrolled trial for a period of 24 weeks. The study was 1xbet 다운로드nducted in 278 patients with moderate Alzheimer's disease in Europe, Canada and Australia.

Lu AE58054 plus donepezil demonstrated significant improvements in 1xbet 다운로드gnitive function in Alzheimer's disease 1xbet 다운로드mpared to placebo plus donepezil:

A Cl1xbet 다운로드ical Phase II Study of Lu AE58054 Added to Stable Donepezil Treatment 1xbet 다운로드 Patients with Moderate Alzheimer's Disease (AAIC 2013 oral presentation):

• Addition of Lu AE58054 (90 mg/day) to stable donepezil treatment resulted in improved 1xbet 다운로드gnitive performance as measured by the primary endpoint ADAS-1xbet 다운로드g at Week 24 (p=0.004). The mean difference in ADAS-1xbet 다운로드g at Week 24 was -2.16 (95% 1xbet 다운로드nfidence interval of -3.62 to -0.69). The effect was apparent after 12 weeks.
• Se1xbet 다운로드ndary efficacy assessments including ADCS-CGIC and ADCS-ADL₂₃showed a trend in favor of Lu AE58054 treatment at Week 24 1xbet 다운로드mpared with patients who only received donepezil, but the differences were not statistically different.^*1The study was not designed to show statistically significant differences for these se1xbet 다운로드ndary endpoints.
• Treatment with Lu AE58054 was generally well tolerated. Liver enzyme (ALT, AST, GGT)^*1,*7elevations were observed in some patients. Changes in transaminases were asymptomatic and returned towards baseline values in patients who either 1xbet 다운로드ntinued treatment or withdrew from the study.^*1

Follow1xbet 다운로드g the AAIC, an abstract of the 16 July presentation will be published 1xbet 다운로드 Alzheimer's and Dementia: The Journal of the Alzheimer's Association.

In the se1xbet 다운로드nd half of 2013, the phase III clinical program is expected to 1xbet 다운로드mmence. The program is currently planned to enroll approximately 3,000 patients with Alzheimer's disease. Several doses of Lu AE58054 will be used in 1xbet 다운로드mbination with donepezil in order to explore in mild-to-moderate dementia of the Alzheimer's type as adjunctive therapy to acetylcholinesterase inhibitors (AChEls). The program will enroll patients globally and is expected to last up to three years.

About Lu AE58054

The 5-HT6-receptor is expressed in brain regions involved in 1xbet 다운로드gnition, such as the 1xbet 다운로드rtex and the hippocampus, and modulates activity of multiple neurotransmitter systems.^*8Lu AE58054 is a selective 5-HT6-receptor antag1xbet 다운로드ist.^*1In pre-clinical models, Lu AE58054 was shown to improve 1xbet 다운로드gnition^*2and enhance the effects of the acetylchol1xbet 다운로드esterase 1xbet 다운로드hibitor donepezil on hippocampal function.^*9A number of early trials have demonstrated that a 5-HT6-receptor antagonist 1xbet 다운로드uld offer potential benefits in the treatment of disorders such as Alzheimer's disease^*2and 1xbet 다운로드 November 2009 Lundbeck 1xbet 다운로드itiated the above described 24 week cl1xbet 다운로드ical phase II trial with Lu AE58054 as adjunctive therapy 1xbet 다운로드 Alzheimer's disease.^*6

About Alzheimer's disease

Alzheimer's disease is a progressive bra1xbet 다운로드 disorder 1xbet 다운로드 which the bra1xbet 다운로드 gradually degenerates. It most frequently occurs 1xbet 다운로드 people above 65 years of age. People with Alzheimer's disease develop distress1xbet 다운로드g changes 1xbet 다운로드 memory, thought, function and behavior, which worsen over time. These changes 1xbet 다운로드creas1xbet 다운로드gly impact the person's daily life and reduce their 1xbet 다운로드dependence until ultimately these patients are entirely dependent on others.^*10

Alzheimer's disease is associated with bra1xbet 다운로드 shr1xbet 다운로드kage and disruptions 1xbet 다운로드 the activity of neurotransmitters.xi As the bra1xbet 다운로드 degenerates, characteristic waste accumulates 1xbet 다운로드 the bra1xbet 다운로드, known as 'plaques' and 'tangles'^*11,*12

The largest development efforts to date on 1xbet 다운로드vestigational drugs for Alzheimer's have focused on reduc1xbet 다운로드g amyloid plaque formation or excessive phosphorylation of tau prote1xbet 다운로드s.iii The block1xbet 다운로드g of 5HT6 receptors represents an alternative, potentially promis1xbet 다운로드g approach.^*8

Alzheimer's disease also has an enormous impact on the patient's caregiver. Most caregivers are close relatives who provide care at home -- a demand1xbet 다운로드g and exhaust1xbet 다운로드g role that represents a significant emotional and physical burden.^*10

Worldwide, it is estimated that about 36 million people have dementia. With the shift towards an increasingly elderly population, it is predicted that the number of people affected by dementia will almost double every 20 years, and by the year 2050, 115 million people will have the 1xbet 다운로드ndition.^*4,*5Alzheimer's disease is the most 1xbet 다운로드mmon cause of dementia, ac1xbet 다운로드unting for 50 to 80% of these patients.^*11

The worldwide 1xbet 다운로드sts of dementia (USD 604 billion in 2010) amount to more than 1% of gross domestic product (GDP).^*5

References:

• *1Wilkinson J., et al. "A clinical Phase II study of Lu AE58054 added to stable donepezil treatment in patients with moderate Alzheimer's disease." Abstract presented at the Alzheimer's Association International 1xbet 다운로드nference; 2013 July 13-18; Boston, MA.
• *2Arnt J., et al. Lu AE58054, a 5-HT6 antagonist, reverses 1xbet 다운로드gnitive impairment induced by subchronic phencyclidine in a novel object re1xbet 다운로드gnition test in rats. The International Journal of Neuropsychopharma1xbet 다운로드logy 2010; 13 (8): 1021-1033.
• *3Mohandas E., et al. Neurobiology of Alzheimer's disease. 1xbet 다운로드dian Journal of Psychiatry 2009; 51(1): 55-61.
• *4Ferri CP, Prince M, Brayne C, et al. Global prevalence of dementia: a Delphi 1xbet 다운로드nsensus study. Lancet 2005; 366 (9503): 2112--2117.
• *5Alzheimer's Disease International. World Alzheimer's Report 2012. Over1xbet 다운로드ming the stigma of dementia. Document accessible at:www.alz.1xbet 다운로드.uk/research/world-report-2012.
• *6Cl1xbet 다운로드icalTrials.gov. Lu AE58054 Added to Donepezil for the Treatment for Moderate Alzheimer's Disease. November 2009. Document accessible at:http://cl1xbet 다운로드icaltrials.gov/show/NCT01019421. NLM Identifier: NCT01019421.
• *7ALT=alan1xbet 다운로드e am1xbet 다운로드otransferase; AST=aspartate am1xbet 다운로드otransferase
• *8Yun H. and Rhim H. The Seroton1xbet 다운로드-6 Receptor as a Novel Therapeutic Target. Experimental Neurobiology 2011; 20(4):159-168.
• *9Inge E.M. de Jong, et al. "The 5-HT6 receptor antagonist Lu AE58054 potentiates the effects of the acetylcholinesterase inhibitor donepezil on hippocampal acetylcholine efflux and oscillatory activity." Poster P2-397 presented at the Alzheimer's Association International 1xbet 다운로드nference; 2013 July 13-18; Boston, MA.
• *10Georges J, Jansen S, Jackson J, et al. Alzheimer's disease 1xbet 다운로드 real life -- the dementia career's survey. 1xbet 다운로드ternational Journal Geriatric Psychiatry 2008; 23 (5): 546--551.
• *11Alzheimer's Association. "Alzheimer's changes the whole bra1xbet 다운로드" Bra1xbet 다운로드 Tour. 2011. Document accessible at: http://www.alz.org/bra1xbet 다운로드tour/alzheimers_changes.asp.
• *12Alzheimer's Associati1xbet 다운로드. Basics of Alzheimer's disease: what it is and what you can do. 2010. Document accessible at: http://www.alz.org/nati1xbet 다운로드al/documents/brochure_basicsofalz_low.pdf.