Lundbeck and Otsuka initiate phase III clinical trials on Lu AE58054 as a new add-on treatment for Alzheimer’s disease

• The clinical program in Alzheimer’s disease is planned to include approximately 3,000 patients from several countries worldwide
• Lu AE58054 is a selective 5-HT6 receptor antagonist under investigation for the treatment of Alzheimer's disease[i]
• The focus of the two companies on the 5-HT6 receptor is a different approach from much of drug research to date on Alzheimer’s disease
• Alzheimer's disease affects more than 26 million people worldwide[ii]. The cost to society has been reported as USD ~600 billion per year[iii]
• Lu AE58054 is the third project the two companies are developing together globally, following Abilify Maintena™ and brexpiprazole

Valby, Denmark and Tokyo, Japan, 10 October 2013 - H. Lundbeck A/S (Lundbeck) and Otsuka Pharmaceutical Co., Ltd. (Otsuka) announced today the continuation of the development program of Lu AE58054 for the treatment of Alzheimer’s disease, initiating the first out of four currently planned phase III clinical trials with the compound in Alzheimer’s disease.                                             

The investigational compound, Lu AE58054 is a selective 5HT6 receptor antagonist with a different proposed mechanism of action than currently available Alzheimer's medications. Notably, a focus on the 5-HT6 receptor is a different approach from the amyloid and tau hypotheses that have underpinned much of the drug research to date on Alzheimer’s disease[iv].

Lundbeck and Otsuka are now initiating the phase III program which is currently planned to consist of four trials. Several doses of Lu AE58054 ranging from 10-60 mg will be used in combination with donepezil in order to explore the effect of the compound in mild-to-moderate Alzheimer’s disease as adjunctive therapy to acetylcholinesterase inhibitors (AChEls). The key endpoints are Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-cog), Activities of Daily Living (ADL), and the Clinical Global Impression of Change Scale (CGIC).           

The program will enroll approximately 3,000 patients worldwide. The first trial will enroll 930 patients in the U.S., Canada and 15 other countries mainly in Europe and is expected to last up to three years.

Data from the phase II clinical study were presented at the Alzheimer’s Association International Conference (AAIC) in July 2013. This study showed that adjunctive therapy with Lu AE58054 (plus 10 mg/day donepezil) at the selected dose resulted in statistically significant improvement in cognitive performance, as measured by the ADAS-cog (Alzheimer's Disease Assessment Scale-cognitive sub-scale) over a 24 week treatment period versus placebo (plus 10mg/day donepezil). Secondary endpoints, including measures of global status and activities of daily living, also showed positive trends with the addition of Lu AE58054 compared with patients who only received donepezil, however the differences were not statistical significant[v].

“Following consultations with different health agencies, with Otsuka we are now ready to start this major program," says Executive Vice President Anders Gersel Pedersen, Head of Research & Development at Lundbeck, and continues: “We believe there is a strong need for more treatment options for patients with Alzheimer's disease, and we see Lu AE58054 as a potentially promising therapy for this devastating disease”

William H. Carson, M.D., President and Chief Executive Officer, Otsuka Pharmaceutical Development and Commercialization, Inc., said, ”Use of the serotonin 5-HT6 antagonism mechanism against the cognitive effects of Alzheimer’s is a promising hypothesis that we will seek to validate more fully in these phase III trials.” 

About Lu AE58054

The 5-HT6-receptor is expressed in brain regions involved in cognition, such as the cortex and the hippocampus, and modulates activity of multiple neurotransmitter systems[vi]. Lu AE58054 is a selective 5-HT6-receptor antagonist. In pre-clinical models, Lu AE58054 was shown to improve cognition and enhance the effects of the acetylcholinesterase inhibitor donepezil on hippocampal function. A number of early trials have demonstrated that a 5-HT6-receptor antagonist could offer potential benefits in the treatment of disorders such as Alzheimer's diseaseⁱ and Lundbeck recently presented the positive results of a 24-week clinical phase II trial with Lu AE58054 as adjunctive therapy in Alzheimer's disease, as mentioned above[vii].

About Alzheimer's disease

Alzheimer's disease is a progressive brain disorder in which the brain gradually degenerates. It most frequently occurs in people above 65 years of age. People with Alzheimer's disease develop distressing changes in memory, thought, function and behaviour, which worsen over time. These changes increasingly impact the person's daily life and reduce their independence until ultimately these patients are entirely dependent on others[viii].

Alzheimer's disease also has an enormous impact on the patient's caregiver. Most caregivers are close relatives who provide care at home — a demanding and exhausting role that represents a significant emotional and physical burden.

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 condition^{II, III}. Alzheimer's disease is the most common cause of dementia, accounting for 50 to 80% of these patients[ix].

The worldwide costs of dementia (estimated at around USD 600 billion in 2010) amount to more than 1% of gross domestic product (GDP).

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About Lundbeck

H. Lundbeck A/S (LUN.CO, LUN DC, HLUYY) is a global pharmaceutical company specialized in brain diseases. For more than 50 years, we have been at the forefront of research within neuroscience. Our development and distribution of pioneering treatments continues to make a difference to people living with brain diseases. Our key areas of focus are alcohol dependence, Alzheimer’s disease, depression/anxiety, epilepsy, Huntington’s disease, Parkinson’s disease, schizophrenia and stroke.

Our 5,800 employees in 57 countries are engaged in the entire value chain throughout research, development, production, marketing and sales, and are committed to improving the quality of life of people living with brain diseases. Our pipeline consists of several late-stage development programs and our products are available in more 100 countries. We have research centers in China, Denmark and the United States, and production facilities in China, Denmark, France, Italy and Mexico. Lundbeck generated revenue of approximately DKK15 billion in 2012 (EUR 2 billion; USD 2.6 billion).

Lundbeck’s shares are listed on the stock exchange in Copenhagen under the symbol ”LUN”. Lundbeck has a sponsored Level 1 ADR program listed in the US (OTC) under the symbol ”HLUYY”. For additional information, we encourage you to visit our corporate site www.lundbeck.com.

About Otsuka Pharmaceutical Co, Ltd.

Otsuka Pharmaceutical Co., Ltd. is a global healthcare company with the corporate philosophy: 'Otsuka-people creating new products for better health worldwide.' Otsuka researches, develops, manufactures and markets innovative and original products, with a focus on pharmaceutical products for the treatment of diseases and nutraceutical products for the maintenance of everyday health.

In pharmaceuticals, Otsuka is a leading firm in the challenging area of mental health and also has research programs on several under-addressed diseases including tuberculosis, a significant global public health issue. These commitments illustrate more powerfully than words how Otsuka is a “big venture” company at heart, applying a youthful spirit of creativity in everything it does.

Otsuka is a wholly owned subsidiary of Otsuka Holdings Co., Ltd., the holding company for the Otsuka Group. The chairman Akihiko Otsuka is the third generation of Otsuka family members to lead the business, whose origins date from 1921. Otsuka products are avaialble in more than 80 countries worldwide and of our nearly 28,000 employees, 20,000 are based outside of Japan. Group Consolidated sales were approximately USD 13 billion for fiscal year 2012 (4/1/2012-3/31/2013). Otsuka warmly invites you to further discover how global the company is at its worldwide website at https://www.otsuka.co.jp/en/.

Safe Harbor/Forward-Looking Statements

The above information contains forward-looking statements that provide our expectations or forecasts of future events such as new product introductions, product approvals and financial performance.

Such forward-looking statements are subject to risks, uncertainties and inaccurate assumptions. This may cause actual results to differ materially from expectations and it may cause any or all of our forward-looking statements here or in other publications to be wrong. Factors that may affect future results include interest rate and currency exchange rate fluctuations, delay or failure of development projects, production problems, unexpected contract breaches or terminations, government-mandated or market-driven price decreases for Lundbeck's products, introduction of competing products, Lundbeck's ability to successfully market both new and existing products, exposure to product liability and other lawsuits, changes in reimbursement rules and governmental laws and related interpretation thereof, and unexpected growth in costs and expenses.

Certain assumptions made by Lundbeck are required by Danish Securities Law for full disclosure of material corporate information. Some assumptions, including assumptions relating to sales associated with product that is prescribed for unapproved uses, are made taking into account past performances of other similar drugs for similar disease states or past performance of the same drug in other regions where the product is currently marketed. It is important to note that although physicians may, as part of their freedom to practice medicine in the US, prescribe approved drugs for any use they deem appropriate, including unapproved uses, at Lundbeck, promotion of unapproved uses is strictly prohibited.

[i] Arnt J., et al. Lu AE58054, a 5-HT6 antagonist, reverses cognitive impairment induced by subchronic phencyclidine in a novel object recognition test in rats. The International Journal of Neuropsychopharmacology 2010; 13 (8): 1021-1033.

[ii] Ferri CP, Prince M, Brayne C, et al. Global prevalence of dementia: a Delphi consensus study. Lancet 2005; 366 (9503): 2112—2117.

[iii] Alzheimer’s Disease International. World Alzheimer’s Report 2012. Overcoming the stigma of dementia.

[iv] Mohandas E., et al. Neurobiology of Alzheimer's disease. Indian Journal of Psychiatry 2009; 51(1): 55–61.

[v] Wilkinson 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 Conference; 2013 July 13-18; Boston, MA.

[vi] Yun H. and Rhim H. The Serotonin-6 Receptor as a Novel Therapeutic Target. Experimental Neurobiology 2011; 20(4):159-168.

[vii] ClinicalTrials.gov. Lu AE58054 Added to Donepezil for the Treatment for Moderate Alzheimer's Disease. November 2009. Document accessible at: http://clinicaltrials.gov/show/NCT01019421. NLM Identifier: NCT01019421.

[viii] Georges J, Jansen S, Jackson J, et al. Alzheimer's disease in real life — the dementia career's survey. International Journal Geriatric Psychiatry 2008; 23 (5): 546—551.

[ix] Alzheimer's Association. “Alzheimer's changes the whole brain” Brain Tour. 2011. Document accessible at: http://www.alz.org/braintour/alzheimers_changes.asp.