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 in 17 countries
*Lu AE58054 is a selective 5-HT receptor antagonist under investigation
for the treatment of Alzheimer's disease^1
*The two companies’ focus on the 5-HT receptor is a different approach
from much of the drug research to date on Alzheimer’s disease^2
*Alzheimer's disease affects more than 26 million people worldwide. The
worldwide cost of Alzheimer's disease and related dementias has been
reported as USD 600 billion per year^3,4
*Lu AE58054 is the third project the two companies are developing together
globally, following Abilify Maintena^TM (aripiprazole) and brexpiprazole
VALBY, Denmark & TOKYO -- October 10, 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 phase
III clinical trials with the compound.
The investigational compound Lu AE58054 is a selective 5-HT receptor
antagonist with a different proposed mechanism of action than currently
available Alzheimer's medications.^1 Notably, a focus on the 5-HT 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.^2
Lundbeck and Otsuka are now initiating the phase III program, which is planned
to include 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 Lu
AE58054 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. 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 (p=0.004) 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 10 mg/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 statistically significant.^5
“Following consultations with different health agencies we are now ready,
together with Otsuka, to start this major program," said Executive Vice
President Anders Gersel Pedersen, Head of Research & Development at Lundbeck,
and continued: “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-HT 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-HT[6 ]receptor is expressed in brain regions involved in cognition, such
as the cortex and the hippocampus, and modulates activity of multiple
Lu AE58054 is a selective 5-HT[6 ]receptor antagonist.^5 In pre-clinical
models, Lu AE58054 was shown to improve cognition^1 and enhance the effects of
the acetylcholinesterase inhibitor donepezil on hippocampal function.^7 A
number of early trials have demonstrated that a 5-HT[6 ]receptor antagonist
could offer potential benefits in the treatment of disorders such as
Alzheimer's disease^1 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.^5,8
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.^9
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.^9
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.^4, 10
Alzheimer's disease is the most common cause of dementia, accounting for 60 to
80% of these patients.^11
The worldwide costs of dementia (USD 604 billion in 2010) amounts to 1% of the
global gross domestic product (GDP).^4
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 than 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
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 Pharmaceutical 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. The Otsuka Group employs approximately 42,000 people
globally and its products are available in more than 80 countries worldwide.
Consolidated sales were approximately USD 13 billion for fiscal year 2012
(4/1/2012-3/31/2013). Otsuka Pharmaceutical warmly invites you to visit its
global website at https://www.otsuka.co.jp/en/.
Arnt J., et al. Lu AE58054, a 5-HT6 antagonist, reverses cognitive
1. impairment induced by subchronic phencyclidine in a novel object
recognition test in rats. The International Journal of
Neuropsychopharmacology 2010; 13 (8): 1021-1033.
2. Mohandas E., et al. Neurobiology of Alzheimer's disease. Indian Journal
of Psychiatry 2009; 51(1): 55–61.
Panza F, et al. γ -Secretase Inhibitors for the Treatment of Alzheimer’s
3. Disease: The Current State. CNS Neuroscience & Therapeutics 2010; 16:
Alzheimer’s Disease International. World Alzheimer’s Report 2012.
4. Overcoming the stigma of dementia. Document accessible at:
Wilkinson J., et al. “A clinical Phase II study of Lu AE58054 added to
5. 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.
6. Yun H. and Rhim H. The Serotonin-6 Receptor as a Novel Therapeutic
Target. Experimental Neurobiology 2011; 20(4):159-168.
Inge E.M. de Jong, et al. “The 5-HT receptor antagonist Lu AE58054
potentiates the effects of the acetylcholinesterase inhibitor donepezil
7. on hippocampal acetylcholine efflux and oscillatory activity.” Poster
P2-397 presented at the Alzheimer's Association International
Conference; 2013 July 13-18; Boston, MA.
ClinicalTrials.gov. Lu AE58054 Added to Donepezil for the Treatment for
8. Moderate Alzheimer's Disease. November 2009. Document accessible at:
http://clinicaltrials.gov/show/NCT01019421. NLM Identifier: NCT01019421.
Georges J, Jansen S, Jackson J, et al. Alzheimer's disease in real life
9. — the dementia career's survey. International Journal Geriatric
Psychiatry 2008; 23 (5): 546—551.
10. Ferri CP, Prince M, Brayne C, et al. Global prevalence of dementia: a
Delphi consensus study. Lancet 2005; 366 (9503): 2112—2117.
Alzheimer's Association. “Alzheimer's changes the whole brain” Brain
11. Tour. 2011. Document accessible at:
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