Elan and Wyeth Announce Encouraging Top-line Results from Phase 2 Clinical Trial of Bapineuzumab for Alzheimer's Disease
• Safety And Efficacy Findings Support Design Of Phase
3 Program
• Primary Efficacy Endpoints In Overall Study Population
Not Statistically Significant
• Statistically Significant And Clinically Meaningful
Benefits Seen In ApoE4 Non-Carriers
• Overall Results Support Prior Decision To Initiate
Phase 3
• Detailed Data Presentation At ICAD July 29, 2008
DUBLIN and MADISON, NJ – June 17, 2008 – Elan
Corporation, plc (NYSE: ELN) and Wyeth (NYSE: WYE) today announced
encouraging preliminary findings from a Phase 2 study of
bapineuzumab (AAB-001) in patients with mild to moderate
Alzheimer's disease. In the 18-month trial, bapineuzumab
appeared to have clinical activity in treating Alzheimer’s
disease.
Efficacy Findings
The study did not attain statistical significance on the primary
efficacy endpoints in the overall study population. Post-hoc
analyses did show statistically significant and clinically
meaningful benefits in important subgroups.
In non-carriers of the Apolipoprotein E4 (ApoE4) allele, estimated in the literature to be from 40 to 70 percent of the Alzheimer’s disease population, post-hoc analyses showed statistically significant and clinically meaningful benefits associated with bapineuzumab treatment on several key efficacy endpoints, including the Alzheimer’s Disease Assessment Scale (ADAS-cog), the Neuropsychological Test Battery (NTB), the Mini Mental State Examination (MMSE) and the Clinical Dementia Rating – Sum of Boxes (CDR-SB). A favorable directional change was seen on the Disability Assessment Scale for Dementia (DAD), although this was not statistically significant.
Additionally in non-carriers, preliminary evaluation of MRI results showed less loss of brain volume among treated patients versus placebo patients, a finding that was statistically significant. Smaller increases in ventricular volume were seen in treated patients compared to placebo patients, although this finding was not statistically significant. Progression of Alzheimer’s disease is generally associated with loss in brain volume and increases in ventricular volume. Further, treatment-related benefits seen on MRI were correlated to the favorable clinical changes observed in non-carriers.
In similar post-hoc analyses of carriers of the ApoE4 allele, no clinical benefits or statistically significant effects were observed on efficacy endpoints or the brain volume endpoint. However, favorable directional changes were observed on a number of endpoints. Preliminary analyses suggest possible increase of ventricular volume in treated patients versus placebo patients. The clinical significance of this finding is currently unclear and analyses are ongoing.
Safety Findings
As expected given the nature of the population studied, adverse
events were very common in both placebo and bapineuzumab-treated
patients. In non-carriers, the number of patients
experiencing serious adverse events was similar between placebo and
bapineuzumab-treated patients. In carriers, serious adverse
events were more frequently observed in bapineuzumab-treated
patients than in placebo patients. In addition, vasogenic
edema was reported in the treated population with an increased
frequency in carriers and at higher doses. No cases were
reported in placebo patients. In the ongoing Phase 3 studies,
carriers of the ApoE4 allele are being treated with a lower dose to
minimize the risk of vasogenic edema. The Companies believe
that the overall safety findings from this Phase 2 trial support
their prior decision to move to Phase 3 studies.
CEO Comments
“The preliminary analyses of the Phase 2 study are a
continued validation of the amyloid approach to Alzheimer's disease
and an important milestone in our companies' ongoing commitment to
bring new treatment options to patients,” said Kelly Martin,
President and CEO of Elan. "These results clinically support
our decision to move into Phase 3 last year."
“We are encouraged by these findings. We remain driven by science and focused on patients as we work to bring this treatment to those who desperately need new options,” said Bernard Poussot, President and CEO, Wyeth. “We recognize there is a great deal of hard work left as we move from this phase of learning towards confirming the potential of bapineuzumab.”
Elan and Wyeth plan to continue all four studies in the previously disclosed bapineuzumab Phase 3 clinical program and will review and discuss these data with regulatory authorities and leading medical experts.
These findings reflect preliminary analyses of the Phase 2 data and its implications for ongoing clinical development of bapineuzumab. In this trial, there were imbalances in patient numbers and characteristics at baseline between subgroups studied that may or may not have affected these results. Further analysis will continue in advance of a planned scientific presentation of detailed results of this study at the International Conference on Alzheimer's Disease (ICAD) in Chicago, July 29, 2008.
About the Trial
The Phase 2 trial was a randomized, double-blind, placebo
controlled, multiple ascending dose study of patients with mild to
moderate Alzheimer's disease. The study was designed to
enroll approximately 240 participants at 29 sites in the United
States. The study tested four doses of bapineuzumab (0.15
mg/kg, 0.5 mg/kg, 1.0 mg/kg and 2.0 mg/kg) with approximately 60
patients in each dose cohort. Patients were randomized on an
8:7 ratio to receive bapineuzumab or placebo, resulting in
approximately 32 participants receiving bapineuzumab and 28
participants receiving placebo in each dose group.
The study assessed the safety of bapineuzumab as well as impact of treatment on cognitive and functional endpoints, biomarkers and blood serum levels. The pre-specified primary efficacy endpoints were change from baseline in ADAS-cog and DAD in the 0.5 mg/kg, 1.0 mg/kg and 2.0 mg/kg dose groups against their placebo cohorts. The study was not powered to detect changes from baseline for the ADAS-Cog or DAD scales. Change in concentrations of tau in cerebral spinal fluid (CSF) was a secondary endpoint. The Neuropsychological Test Battery, Clinical Dementia Rating Sum of Boxes and Mini Mental State Examination (MMSE) were included as tertiary efficacy endpoints. Efficacy was assessed from baseline for 18 months.
About Bapineuzumab
Bapineuzumab is the first humanized monoclonal antibody in
late-stage investigation as a potential treatment for
Alzheimer’s disease. Bapineuzumab is designed to clear
toxic beta amyloid from the brain. The beta amyloid protein
is a key component of the neuritic plaques that are implicated in
the pathology of Alzheimer’s disease. A global Phase 3
clinical program was initiated in December 2007 and is intended to
provide safety and efficacy data to support the filing and approval
of licensing applications for bapineuzumab as a potential treatment
for patients with mild to moderate Alzheimer’s disease.
To learn more about this enrollment, patients or caregivers should
contact clinical sites directly. Participating clinical sites
can be found by visiting www.icarastudy.com or, in the
United States by calling 1 (888) 818-MEMORY. Study site
details also can be found by visiting www.clinicaltrials.gov.
About Alzheimer’s Disease
Alzheimer’s disease 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,
such as bathing and eating. 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. As many as 5 million
Americans are estimated to have Alzheimer’s disease, and more
than 26 million people worldwide. One in eight baby boomers
will develop the disease and half of all people after 85 and
older.
About the Elan and Wyeth Collaboration
The Wyeth and Elan Alzheimer's Immunotherapy Program (AIP) includes
investigational clinical programs for bapineuzumab. AIP is a
collaboration between the two Companies to research, develop and
commercialize immunotherapeutic approaches that may be used to
treat and possibly prevent the onset of Alzheimer’s
disease. AIP research focuses on the beta amyloid hypothesis,
as the Companies believe that enhancing the clearance of beta
amyloid in the brain may provide a new treatment approach for
Alzheimer’s disease.
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 Wyeth
Wyeth Pharmaceuticals, a division of Wyeth, has leading products in
the areas of women’s health care, infectious disease,
gastrointestinal health, central nervous system, inflammation,
transplantation, hemophilia, oncology, vaccines and nutritional
products.
Wyeth is one of the world’s largest research-driven pharmaceutical and health care products companies. It is a leader in the discovery, development, manufacturing and marketing of pharmaceuticals, vaccines, biotechnology products, nutritionals and non-prescription medicines that improve the quality of life for people worldwide. The Company’s major divisions include Wyeth Pharmaceuticals, Wyeth Consumer Healthcare and Fort Dodge Animal Health. For additional information about the company, please visit http://www.wyeth.com.
Safe Harbor/Forward-Looking Statements
The statements in this press release regarding the Companies’
preliminary, top-line assessment of the Phase 2 data and its
implications for the Phase 3 program and future development of
bapineuzumab are forward-looking statements that are subject to
risks and uncertainties that could cause actual results to differ
materially from those expressed or implied by such
statements. In particular, these statements are subject to
the risk that further analyses of the Phase 2 data may lead to
different (including less favorable) interpretations of the data
than the preliminary analyses conducted to date and/or may identify
important implications of the Phase 2 data that are not reflected
in these statements. Clinical trial data are subject to
differing interpretations, and regulatory agencies, medical and
scientific experts and others may not share the Companies’
views of the Phase 2 data or its implications for the Phase 3
program and future development of bapineuzumab. In addition,
further analyses of the Phase 2 data and discussion with regulatory
authorities may lead to important modifications to the Phase 3
program. There can be no assurance that the clinical program
for bapineuzumab will be successful in demonstrating safety and/or
efficacy, that we will not encounter problems or delays in clinical
development, or that bapineuzumab will ever receive regulatory
approval or be successfully commercialized. Other risks and
uncertainties that could cause actual results to differ materially
from those expressed or implied by these forward-looking statements
include those detailed from time to time in the Companies’
periodic reports filed with the Securities and Exchange Commission,
including Wyeth's current reports on Form 8-K, quarterly reports on
Form 10-Q and annual report on Form 10-K, particularly the
discussion under the caption "Item 1A, Risk Factors" in Wyeth's
Annual Report on Form 10-K for the year ended December 31, 2007,
which was filed with the Securities and Exchange Commission on
February 29, 2008, and Elan's Reports of Foreign Issuer on Form 6-K
and Annual Report on Form 20-F, particularly the discussion under
the caption “Item 3D, Risk Factors” in Elan’s
Annual Report on Form 20-F for the year ended December 31, 2007,
which was filed with the Securities and Exchange Commission on
February 28, 2008. The forward-looking statements in this
press release are qualified by these risk factors. We assume
no obligation to publicly update any forward-looking statements,
whether as a result of new information, future developments or
otherwise.
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INVESTOR CONTACTS: |
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Elan Chris Burns Ph: 800 252 3526 David Marshall Ph: 353 1 709 4444 |
Wyeth Justin Victoria Ph: 973-660-5340 |
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MEDIA CONTACTS: |
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Elan Jonathan Birt Ph: 212 850 5664 44 20 7269 7205 Niamh Lyons Ph: 353 1 663 3602 |
Wyeth Douglas Petkus Ph: 973-660-5218 Michael Lampe Ph: 484-865-1346 |
