Co-Primary Clinical Endpoints Not Met in Study of Patients with
Alzheimer’s Disease Who Carry The ApoE4 Genotype
Pfizer
Inc. (NYSE: PFE) announced today that the co-primary
clinical endpoints, change in cognitive and functional performance
compared to placebo, were not met in the Janssen Alzheimer Immunotherapy
R&D LLC (Janssen AI)-led Phase 3 trial of intravenous (IV) bapineuzumab
in patients with mild-to-moderate Alzheimer’s disease who carry the
ApoE4 (apolipoprotein E epsilon 4) genotype (Study 302). Pfizer and
Janssen AI are partners in the Alzheimer’s Immunotherapy Program
(AIP).
These clinical findings have been shared with regulatory authorities and
study investigators so that participants in the ongoing clinical program
can be informed. Because in this study clinical efficacy was not
demonstrated in ApoE4 carriers, the Janssen AI and Pfizer Joint Steering
Committee for the AIP has decided that participants from this study who
enrolled in a follow-on extension study will no longer receive doses of
bapineuzumab. However, these patients will have a follow-up evaluation.
Based on a comprehensive review of the data by the independent safety
monitoring committee, all other ongoing Janssen AI and Pfizer
bapineuzumab studies are continuing as planned and without modifications.
Study 302 is the first of four placebo-controlled Phase 3 studies to
complete in the comprehensive development program of bapineuzumab IV.
Janssen AI is leading two Phase 3 studies of patients who are ApoE4
carriers (Study 302) and non-carriers (Study 301) at sites primarily in
North America. Pfizer is conducting two Phase 3 studies of patients who
are ApoE4 carriers (Study 3001) and non-carriers (Study 3000) at sites
primarily outside of North America.
The Alliance will expedite the completion of an interim analysis for the
on-going, Pfizer-conducted Phase 3 study of ApoE4 carriers (Study 3001)
based on the results of Study 302.
The topline results from Study 301 in patients with mild-to-moderate
Alzheimer’s disease who do not carry the ApoE4 genotype are expected to
be announced later this summer.
“While we are disappointed in the topline results of Study 302, a more
complete understanding of bapineuzumab and its potential utility in
mild-to-moderate Alzheimer’s disease will be gained following the
availability of additional data, including data from the soon-to-be
available non-carrier Study 301,” said Steven J. Romano, M.D., senior
vice president, head, Medicines Development Group, Global Primary Care
Business Unit, Pfizer Inc. “We recognize that Alzheimer’s disease is
very complex, but Pfizer, along with our partner Janssen AI, remains
committed to advancing the science of Alzheimer’s disease, with the
ultimate goal of delivering innovative and meaningful new treatment
options to patients.”
Data from both the ApoE4 carrier (Study 302) and non-carrier (Study 301)
studies have been accepted as a late-breaker and will be presented in
September at the European Federation of Neurological Societies meeting
in Stockholm.
The presence of the ApoE epsilon 4 genotype is a genetic risk factor for
Alzheimer’s disease and is associated with increased beta-amyloid
plaques in the brains of patients with the disease. Topline results of
Study 302 indicate that among patients treated with bapineuzumab IV the
most commonly observed serious adverse events which occurred more
commonly than placebo and with an incidence of at least 1 percent were
ARIA-E and dehydration. ARIA-E (amyloid-related imaging
abnormalities-edema or effusion) refers to changes in the brain that may
be due to fluid (water and protein) leaking from blood vessels, which
can be detected using magnetic resonance imaging (MRI) of the brain.
About the Bapineuzumab IV Phase 3 Studies
There are four placebo-controlled Phase 3 studies in the bapineuzumab
clinical development program. Janssen AI is leading two 18-month, Phase
3, multicenter, randomized, double-blind, placebo-controlled,
parallel-group, efficacy and safety studies of patients who are ApoE4
carriers (Study 302) and Apoe4 non-carriers (Study 301). The two
co-primary clinical endpoints are change in the Alzheimer's Disease
Assessment Scale-Cognitive subscale (ADAS-Cog), a validated measure of
cognition, and the Disability Assessment for Dementia (DAD), a validated
instrument to measure function. Study 302 included approximately 1,100
patients who carry the ApoE4 genotype and Study 301 includes
approximately 1,300 patients who do not carry the ApoE4 genotype.
In addition to the Janssen AI-led studies, Pfizer is conducting two
primarily ex-North America 18-month, Phase 3, multicenter, randomized,
double-blind, placebo-controlled, parallel-group, efficacy and safety
studies of patients with mild-to-moderate Alzheimer’s disease who are
ApoE4 non-carriers (Study 3000) and carriers (Study 3001).
About Bapineuzumab IV
Bapineuzumab IV, an investigational therapy being studied for the
treatment of mild-to-moderate Alzheimer’s disease, is an antibody that
targets beta-amyloid (Aβ), a protein that can exert toxic effects in the
brain and is believed to play a central role in the pathology of
Alzheimer’s disease.
About Alzheimer’s disease
Alzheimer’s disease, the most common form of dementia, is a degenerative
brain disease that is not a normal part of aging. Currently there is
neither a cure nor a treatment that delays the course of Alzheimer’s
disease, which gradually destroys a person’s cognitive and functional
abilities, including memory and the ability to perform activities of
daily living, such as bathing and eating. Alzheimer’s disease is the
sixth leading cause of death in the United States, estimated to affect
more than five million people. It is estimated that there were 35.6
million people with dementia, including Alzheimer’s disease, worldwide
in 2010. This number is projected to nearly double every 20 years,
increasing to 65.7 million in 2030 and 115.4 million in 2050 worldwide.
Furthermore, the total worldwide costs of dementia, including
Alzheimer's disease, were estimated around one percent of global gross
domestic product (GDP) in 2010, at more than US$600 billion. This
includes costs attributed to informal unpaid care, community or
residential-based care and treatment.
About the Alzheimer’s Immunotherapy Program
The Alzheimer's Immunotherapy Program of Janssen Alzheimer Immunotherapy
and Pfizer Inc. is an equal collaboration committed to researching and
developing selective products for the treatment and/or prevention of
neurodegenerative conditions, including Alzheimer’s disease.
We believe that it is possible to reduce the burden of disease through
early intervention in the illness. The AIP is dedicated to delivering
comprehensive and integrated solutions that help address the needs of
people impacted by Alzheimer’s disease.
Pfizer Inc.: Working together for a healthier world™
At Pfizer, we apply science and our global resources to improve health
and well-being at every stage of life. We strive to set the standard for
quality, safety and value in the discovery, development and
manufacturing of medicines for people and animals. Our diversified
global health care portfolio includes human and animal biologic and
small molecule medicines and vaccines, as well as nutritional products
and many of the world’s best-known consumer products. Every day, Pfizer
colleagues work across developed and emerging markets to advance
wellness, prevention, treatments and cures that challenge the most
feared diseases of our time. Consistent with our responsibility as the
world’s leading biopharmaceutical company, we also collaborate with
health care providers, governments and local communities to support and
expand access to reliable, affordable health care around the world.
For more than 150 years, Pfizer has worked to make a difference for all
who rely on us.
DISCLOSURE NOTICE: The information contained in this release is
as of July 23, 2012. Pfizer assumes no obligation to update
forward-looking statements contained in this release as the result of
new information or future events or developments.
This release contains forward-looking information about a product
candidate, bapineuzumab, including its potential benefits, that involves
substantial risks and uncertainties. Such risks and uncertainties
include, among other things, the uncertainties inherent in research and
development, including the ability to meet anticipated clinical trial
completion dates and regulatory submission dates; whether and when any
drug applications may be filed in any jurisdictions for bapineuzumab;
whether and when any such applications may be approved by regulatory
authorities as well as their decisions regarding labeling and other
matters that could affect its availability or commercial potential; and
competitive developments.
A further description of risks and uncertainties can be found in
Pfizer’s Annual Report on Form 10-K for the fiscal year ended December
31, 2011 and in its reports on Form 10-Q and Form 8-K.
