Presentations at 2009 Alzheimer’s Association International
Conference on Alzheimer’s Disease Support Ongoing Phase 2 Trial
Elan and Transition Therapeutics Announce Phase 1 Data Showing
ELND005 Achieves Desired Concentrations in Brain Tissue and
Cerebrospinal Fluid
Elan Corporation PLC
Elan Corporation, plc (NYSE: ELN) and Transition Therapeutics Inc. (TSX:
TTH, NASDAQ: TTHI) today presented Phase 1 data demonstrating that
treatment with ELND005 (scyllo-inositol formerly known as AZD-103),
achieves desired concentrations in human brain tissue and cerebrospinal
fluid when given orally. Preclinical data also were presented showing
that ELND005 administration is associated with preservation of choline
acetyltransferase (ChAT), reflecting preservation of nerve cells that
are critical to memory function in the brain. ELND005 is an
orally-administered drug candidate in Phase 2 trials for the treatment
of mild to moderate Alzheimer’s disease. These results were presented at
the 2009 Alzheimer’s Association International Conference on Alzheimer’s
Disease (ICAD 2009) in Vienna, Austria.
In a poster entitled, “Oral Amyloid Anti-aggregating Agent ELND005 is
Measurable in CSF and Brain of Healthy Adult Men,” the researchers
describe results of a Phase 1 study in which eight healthy adults each
received 2,000 mg of ELND005 twice a day for 10 days. Concentrations of
ELND005 in cerebrospinal fluid were measured directly, while brain
tissue concentrations were measured non-invasively using a novel
magnetic resonance spectroscopy technique and were determined to be
within the range associated with efficacy in previous animal studies
that employed a transgenic animal model of Alzheimer’s Disease. ELND005
was well tolerated by these study participants with no severe, serious,
or treatment-limiting adverse events observed.
“Achieving a clinically beneficial concentration of drug in brain tissue
and cerebrospinal fluid has presented a significant hurdle to other
drugs investigated to treat Alzheimer’s Disease, so this is an important
proof of concept for us,” said Elan president Carlos V. Paya, MD, PhD.
“We look forward to completing and reporting results from our ongoing
Phase 2 study of ELND005 in patients with mild to moderate Alzheimer's
disease, which completed enrollment in October 2008.”
In a second poster, entitled “Quantification of Cholinergic Degradation
and Adult Neurogenesis in TgCRND8 Mice Following Treatment with
Scyllo-Inositol (ELND005),” Dr. JoAnne McLaurin and colleagues from the
University of Toronto analyzed levels of the enzyme Choline
Acetyltransferase (ChAT) in an animal model of Alzheimer’s disease. As
in humans, these Alzheimer’s animal models exhibit damage to nerve cells
in a region of the brain called the “basal forebrain” that use the
neurotransmitter acetylcholine to transmit nerve impulses critical to
memory functions to other nerve cells in a brain region important for
memory function called the hippocampus. Animals treated with ELND005
exhibited significantly more ChAT levels compared to untreated animals.
“There is evidence that amyloid plaque formation drives the decline in
memory and cognition associated with Alzheimer’s disease,” said JoAnne
McLaurin, PhD, professor at the University of Toronto’s Centre for
Research in Neurodegenerative Diseases. “Although more research is
necessary, the findings presented today suggest that ELND005 may have
the ability to prevent the loss of ChAT that results from damage to
cholinergic neurons in the brain, thereby potentially protecting against
cognitive decline in individuals with Alzheimer’s disease.”
“We have conducted a robust preclinical and Phase 1 research program of
ELND005 that has demonstrated that the drug is able to cross the
blood-brain barrier, which should allow it to target the disaggregation
of amyloid beta in the brain,” said Dr. Tony Cruz, chairman and chief
executive officer of Transition.
In 2006, Elan and Transition entered into an exclusive, worldwide
collaboration agreement for the joint development and commercialization
of ELND005 for the treatment of Alzheimer’s disease and other
indications.
About ELND005 (AZD-103)
ELND005 is an orally-administered therapeutic agent that has received
fast track designation from the U.S. Food and Drug Administration (FDA)
for treatment of mild to moderate Alzheimer’s disease. Fast track
designation can facilitate development and may expedite regulatory
review of drugs that the FDA recognizes as potentially addressing an
unmet medical need for serious or life-threatening conditions.
ELND005 is currently in a Phase 2 clinical study, which completed
enrollment in October 2008. The study is a randomized, double-blind,
placebo-controlled, dose-ranging, safety and efficacy study in
approximately 340 patients with mild to moderate Alzheimer’s disease.
The planned treatment period for each patient is approximately 18 months.
About Alzheimer’s Disease
Alzheimer’s disease, a leading cause of dementia, is a progressive brain
disorder that gradually destroys a person's memory and ability to learn,
reason, make judgments, communicate and carry out daily activities.
Alzheimer’s disease may result from the build-up of toxic beta-amyloid
peptides in the brain. As Alzheimer’s disease progresses, individuals
may also experience changes in personality and behavior, such as
anxiety, suspiciousness or agitation, as well as delusions or
hallucinations. It is currently estimated that more than 5 million
Americans have Alzheimer’s disease and more than 24 million people
worldwide over the age of 60 have some form of dementia (Source:
Alzheimer’s Association and Alzheimer’s Disease International).
About Elan
Elan Corporation, plc is a neuroscience-based biotechnology company
committed to making a difference in the lives of patients and their
families by dedicating itself to bringing innovations in science to fill
significant unmet medical needs that continue to exist around the world.
Elan shares trade on the New York, London and Dublin Stock Exchanges.
For additional information about the company, please visit http://www.elan.com.
About Transition
Transition is a biopharmaceutical company, developing novel therapeutics
for disease indications with large markets. Transition's lead products
include ELND005 for the treatment of Alzheimer's disease and TT-223 for
the treatment of diabetes. Transition has an emerging pipeline of
preclinical drug candidates acquired externally and developed internally
using its proprietary drug discovery engine. Transition's shares are
listed on the NASDAQ under the symbol 'TTHI' and the Toronto Stock
Exchange under the symbol 'TTH'. For additional information about the
Company, please visit www.transitiontherapeutics.com.
Safe Harbor/Forward-Looking Statements
This press release contains forward-looking statements regarding the
development of scyllo-inositol (ELND005) under the collaboration
agreement between Elan and Transition. These statements are based on
Elan’s and Transition's current beliefs and expectations. ELND005 may
not be successfully developed or commercialized under the collaboration
agreement. Factors which could cause actual results to differ materially
from Elan’s and Transition's current expectations include the risks that
clinical development of ELND005 fails due to safety or efficacy issues,
the results from Phase 1 clinical trials and preclinical testing of
ELND005 are not predictive of results to be obtained in Phase 2 or later
clinical trials, the patent issued with respect to ELND005 may not
provide substantial protection or commercial benefit, the development
and commercialization of competitive therapies, the collaboration
agreement is terminated early or Elan and Transition encounter other
unexpected delays or hurdles. Drug development and commercialization
involves a high degree of risk.
For more detailed information on the risks and uncertainties associated
with Elan and Transition's drug development and other activities, see
the periodic and current reports that Elan has filed with the Securities
and Exchange Commission and that Transition has filed with the
Securities and Exchange Commission and the Ontario Securities
Commission. Elan and Transition assume no obligation to update any
forward-looking statements, whether as a result of new information,
future events or otherwise.
