Study Results of GAMMAGARD S/D and GAMMAGARD LIQUID in Patients with Mild-to-Moderate...

Study Results of GAMMAGARD S/D and GAMMAGARD LIQUID in Patients with
Mild-to-Moderate Alzheimer's Disease Announced
Phase II data from study of GAMMAGARD-treated patients announced at the
American Academy of Neurology annual meeting

CHICAGO, April 17 /PRNewswire-FirstCall/ -- New York-Presbyterian
Hospital/Weill Cornell Medical Center and Baxter International Inc.
(NYSE: BAX) announced results of a six-month, placebo-controlled Phase II
study of 24 patients treated with GAMMAGARD S/D and GAMMAGARD LIQUID [Immune
Globulin Intravenous (IGIV)] for the treatment of mild-to-moderate Alzheimer's
disease today at the American Academy of Neurology (AAN) annual meeting in
Chicago. The study met the primary endpoint criteria favoring GAMMAGARD LIQUID
and GAMMAGARD S/D over placebo on measures of cognitive function and global
impression of change, which are common measures of outcome in Alzheimer's
disease clinical trials. The study also met secondary endpoints that measured
changes in beta-amyloid and anti-amyloid antibody levels in blood and
cerebrospinal fluid. Results show findings indicative of potential efficacy
and tolerability. Key findings throughout six months included: measurements of
clinical outcome, behavioral outcome and cognitive performance in Alzheimer's
patients treated with GAMMAGARD S/D and GAMMAGARD LIQUID compared to placebo.
Twelve-to-18 month data will be available later this year.
Secondary endpoint results suggest that levels of antibodies against
beta-amyloid were observed to have increased in the blood and cerebrospinal
fluid of patients treated with GAMMAGARD S/D and GAMMAGARD LIQUID, while the
levels of beta-amyloid increased in the blood. Beta-amyloid is a substance
thought to contribute to the degeneration of the brain in Alzheimer's disease.
Clearing this substance from the central nervous system, therefore is
hypothesized to help remove or reduce the building blocks of Alzheimer's.
The primary and secondary endpoint data were reported by the lead
researcher for the trial, Dr. Norman Relkin, director of the Memory Disorders
Program and behavioral neurologist and neuroscientist at New
York-Presbyterian/Weill Cornell Medical Center, and associate professor of
clinical neurology at Weill Cornell Medical College in New York City.
"This was the first placebo-controlled clinical trial of GAMMAGARD for
Alzheimer's disease and the results are clearly promising," Dr. Relkin
commented.
Baxter supported the study and provided GAMMAGARD LIQUID and GAMMAGARD S/D
for the trial. GAMMAGARD S/D and GAMMAGARD LIQUID, marketed as KIOVIG in the
European Union, contain a broad spectrum of immunoglobulins (antibodies) and
are indicated as an immunoglobulin replacement therapy that boosts the immune
system in patients with primary immunodeficiency disorders. The precise
mechanisms of GAMMAGARD S/D and GAMMAGARD LIQUID's effects in Alzheimer's
disease are not known.
"These study results reflect Baxter's support of innovative science and
commitment to meeting a critical, unmet medical need," said Hartmut J.
Ehrlich, MD, vice president of global research and development for Baxter's
BioScience business. "While results of Baxter's mid-stage development work in
Alzheimer's disease treatment are promising, further investigation in a larger
Phase III study is required."
Phase II Study Design
In the double-blind, placebo-controlled Phase II study, 24 patients in the
United States with mild-to-moderate Alzheimer's disease, who were maintained
on standard treatment therapy, were randomly assigned to receive GAMMAGARD
LIQUID (eight patients), GAMMAGARD S/D (eight patients) or saline placebo
(eight patients) for six months. The study included a comparison of four
dosing regimens of GAMMAGARD, with doses ranging from 0.2 g/kg every two weeks
to 0.8 g/kg every month. The safety and tolerability of the treatment and
clinical outcomes of 24 patients were assessed at the beginning of the study
and after three and six months. The study is an ongoing, open-label study
extended to 18 months to examine the long-term effects of the treatment.
Cognitive, behavioral and functional measures were collected at baseline,
three months and six months of treatment. The primary endpoints of the Phase
II trial were cognitive function (as measured by the ADAS-cog) and global
impression of change (as assessed by the Alzheimer's Disease Cooperative
Study-Clinical Global Impression of Change (ADCS-CGIC) change rating). The
secondary endpoints measured changes in beta-amyloid and anti-amyloid antibody
levels in blood and cerebrospinal fluid. Safety and tolerability of GAMMAGARD
S/D and GAMMAGARD LIQUID treatment in Alzheimer's patients were also assessed
relative to placebo.
Phase II Study Results
In August 2007, Baxter and New York-Presbyterian/Weill Cornell announced
preliminary Phase II results based on six-month data, indicating the study
provided encouragement to carry out a Phase III trial. The criteria for going
forward with a Phase III trial were favorable outcomes in GAMMAGARD S/D and
GAMMAGARD LIQUID-treated patients relative to those given placebo. The final
results of the study re-affirm the decision of Baxter and the ADCS to pursue a
multi-center, Phase III study evaluating the role of GAMMAGARD LIQUID for the
treatment of patients with mild-to-moderate Alzheimer's disease. The decision
was based on results of two completed, open-label clinical studies and the
preliminary six-month interim analysis of the Phase II trial.
The Phase II study follows an earlier Phase I study in eight patients
carried out at New York-Presbyterian/Weill Cornell that was published in the
journal Neurobiology of Aging in February 2008.
Cognitive Function and Global Impression of Change Findings (Primary
Endpoints)
After six months, the group of patients treated with GAMMAGARD S/D and
GAMMAGARD LIQUID averaged 1.52 points higher than placebo-treated patients
(+0.27 versus -1.25) on the ADCS-CGIC score, a commonly used measure of
outcome in Alzheimer's disease clinical trials. The ADCS-CGIC is used in
Alzheimer's trials to assess clinically relevant overall changes in
Alzheimer's disease patients determined by patient and caregiver interviews.
Patients treated with GAMMAGARD S/D and GAMMAGARD LIQUID had fewer
behavior-related adverse events during the six-month trial and had a more
favorable behavioral outcome as measured by the Neuropsychiatric Inventory, a
scale used to measure behavioral problems in Alzheimer's patients. The average
change in ADAS-Cog score -- a common cognitive testing measure -- at six
months of treatment was numerically improved in patients treated with
GAMMAGARD S/D and GAMMAGARD LIQUID than placebo (-0.38 versus +2.61), although
this difference did not reach statistical significance in the relatively small
number of patients studied.
Levels of Beta-Amyloid (Secondary Endpoints)
Dr. Relkin also reported observations that levels of antibodies against
beta-amyloid increased in the cerebrospinal fluid and blood of patients
treated with GAMMAGARD S/D and GAMMAGARD LIQUID, while the levels of
beta-amyloid in the blood increased. The antibody and beta-amyloid levels were
assessed using ELISA immunosorbant assay, a method used to detect antibodies,
and observations were analyzed using parametric statistical analysis.
Tolerability
The study also met its endpoint in assessing the tolerability of GAMMAGARD
S/D and GAMMAGARD LIQUID in Alzheimer's patients. The only treatment-related
adverse events that occurred at a greater frequency with GAMMAGARD S/D and
GAMMAGARD LIQUID treatment as compared to placebo were rash and a transient
drop in blood count (in most cases, hemoglobin (Hgb) levels returned to within
1 Hgb unit of baseline within three to six months).
Brain Metabolism (Additional, Observational Finding)
Dr. Lisa Mosconi, assistant professor of psychiatry at New York University
Medical Center, worked with the New York-Presbyterian/Weill Cornell group on
the analysis of brain imaging data from the study and also presented findings
at the AAN meeting. She reported that GAMMAGARD-treated participants had
observable changes in brain metabolism. While energy metabolism in the brain
was an exploratory endpoint in the study it was preserved or improved in 10
out of 13 patients after six months of GAMMAGARD S/D and GAMMAGARD LIQUID
treatment.
"Brain metabolism usually decreases progressively in patients with
Alzheimer's disease," said Dr Mosconi. "The changes on PET scans of these
Alzheimer's patients after six months of GAMMAGARD S/D and GAMMAGARD LIQUID
are encouraging."
The Phase II study also evaluated brain metabolism in patients treated
with GAMMAGARD S/D and GAMMAGARD LIQUID compared to those who received placebo
based on 18F-fluoro-deoxyglucose Positron Emission Tomography (PET) (FDG-PET)
scans, which are sometimes used in the diagnosis of Alzheimer's disease.
Across brain regions usually affected by Alzheimer's disease, in this study
the GAMMAGARD S/D and GAMMAGARD LIQUID groups were observed to show 16 percent
higher brain metabolism after treatment compared to placebo (12-18 percent
increase in the hippocampi, 14-17 percent increase in parieto-temporal
cortices and 21-24 percent increase in the thalami).
Phase III Study
The Phase III study is sponsored by the National Institutes of Health
(NIH) and Baxter. The study protocol was submitted to the U.S. Food and Drug
Administration for review, with the intention of initiating patient
recruitment later in 2008. The trial will include approximately 35 leading
academic centers in the United States that are members of the Alzheimer's
Disease Cooperative Study (ADCS). The involvement of the ADCS and NIH in the
conduct of the Phase III trial will ensure the highest level of independent
scientific evaluation of the potential role of GAMMAGARD S/D and GAMMAGARD
LIQUID in the treatment of Alzheimer's.
About Alzheimer's Disease
Alzheimer's disease is the most common form of dementia, a clinical
condition that involves the decline or loss of memory and other cognitive
abilities. A progressive and ultimately fatal disease marked by severe brain
tissue deterioration, Alzheimer's disease initially involves the parts of the
brain that control thought, memory and language. According to the Alzheimer's
Association, an estimated 5.2 million American have Alzheimer's, including one
out of eight people age 65 and older. The number of new Alzheimer's disease
cases diagnosed annually is expected to reach 454,000 by 2010, with 959,000
new cases a year by 2050. By that time, the number of people age 65 and older
with Alzheimer's disease could reach as high as 16 million.
About GAMMAGARD LIQUID and GAMMAGARD S/D
GAMMAGARD LIQUID
GAMMAGARD LIQUID is indicated for the treatment of primary
immunodeficiency disorders associated with defects in humoral immunity. These
include but are not limited to congenital X-linked agammaglobulinemia, common
variable immunodeficiency, Wiskott-Aldrich syndrome, and severe combined
immunodeficiencies.
Important Safety Information
GAMMAGARD LIQUID is contraindicated in patients with known anaphylactic or
severe hypersensitivity responses to Immune Globulin (Human). Patients with
severe selective IgA deficiency (IgA < 0.05 g/L) may develop anti-IgA
antibodies that can result in a severe anaphylactic reaction.
Immune Globulin Intravenous (Human) products have been reported to be
associated with renal dysfunction, acute renal failure, osmotic nephrosis, and
death. Patients predisposed to acute renal failure include patients with any
degree of pre-existing renal insufficiency, diabetes mellitus, age greater
than 65, volume depletion, sepsis, paraproteinemia, or patients receiving
known nephrotoxic drugs. Especially in such patients, IGIV products should be
administered at the minimum concentration available and the minimum rate of
infusion practicable. While these reports of renal dysfunction and acute renal
failure have been associated with the use of many of the licensed IGIV
products, those containing sucrose as a stabilizer accounted for a
disproportionate share of the total number.
Glycine, an amino acid, is used as a stabilizer. GAMMAGARD LIQUID does not
contain sucrose.
GAMMAGARD LIQUID is made from human plasma. It may carry a risk of
transmitting infectious agents, viruses, and theoretically, the Creutzfeldt-
Jakob disease (CJD) agent.
Components used in the packaging of this product are latex-free.
Thrombotic events have been reported in association with IGIV. Patients at
risk may include those with a history of atherosclerosis, multiple
cardiovascular risk factors, advanced age, impaired cardiac output, and/or
known or suspected hyperviscosity, hypercoagulable disorders, and prolonged
periods of immobilization.
IGIV products can contain blood group antibodies that may cause a positive
direct antiglobulin reaction and, rarely, hemolysis.
Aseptic meningitis syndrome (AMS) has been reported to occur infrequently
in association with IGIV treatment. Discontinuation of IGIV treatment has
resulted in remission of AMS within several days without sequelae.
Various mild and moderate reactions, such as headache, fever, fatigue,
chills, flushing, dizziness, urticaria, wheezing or chest tightness, nausea,
vomiting, rigors, back pain, chest pain, muscle cramps, and changes in blood
pressure may occur with infusions of Immune Globulin Intravenous (Human).
For full prescribing information, please visit
http://www.gammagardliquid.com.
GAMMAGARD S/D [Immune Globulin Intravenous (Human)]
GAMMAGARD S/D is indicated for the treatment of primary immunodeficiency
disorders associated with defects in humoral immunity. These include but are
not limited to congenital X-linked agammaglobulinemia, common variable
immunodeficiency, Wiskott-Aldrich syndrome, and severe combined
immunodeficiencies.
GAMMAGARD S/D must not be used in patients with selective IgA deficiency
(IgA < 0.05 g/L) where the IgA deficiency is the only abnormality of concern.
Important Safety Information
Patients may experience severe hypersensitivity reactions or anaphylaxis
in the setting of detectable IgA levels following infusion of GAMMAGARD S/D.
Immune Globulin Intravenous (Human) products have been reported to be
associated with renal dysfunction, acute renal failure, osmotic nephrosis, and
death. Patients predisposed to acute renal failure include patients with any
degree of pre-existing renal insufficiency, diabetes mellitus, age greater
than 65, volume depletion, sepsis, paraproteinemia, or patients receiving
known nephrotoxic drugs. Especially in such patients, IGIV products should be
administered at the minimum concentration available and the minimum rate of
infusion practicable. While these reports of renal dysfunction and acute renal
failure have been associated with the use of many of the licensed IGIV
products, those containing sucrose as a stabilizer accounted for a
disproportionate share of the total number.
GAMMAGARD S/D does not contain sucrose.
GAMMAGARD S/D is made from human plasma. It may carry a risk of
transmitting infectious agents, e.g. viruses, and theoretically, the
Creutzfeldt-Jakob disease (CJD) agent.
Aseptic meningitis syndrome (AMS) has been reported to occur infrequently
in association with IGIV treatment. Discontinuation of IGIV treatment has
resulted in remission of AMS within several days without sequelae.
Certain components used in the packaging of GAMMAGARD S/D contain natural
rubber latex.
IGIV products can contain blood group antibodies that may cause a positive
direct antiglobulin reaction and, rarely, hemolysis.
Thrombotic events have been reported in association with IGIV. Patients at
risk may include those with a history of atherosclerosis, multiple
cardiovascular risk factors, advanced age, impaired cardiac output, and/or
known or suspected hyperviscosity, hypercoagulable disorders, and prolonged
periods of immobilization.
Various minor reactions, such as mild to moderate hypotension, headache,
fatigue, chills, backache, leg cramps, lightheadedness, fever, urticaria,
flushing, slight elevation of blood pressure, nausea and vomiting, may
occasionally occur.
For full prescribing information, please visit:
http://www.immunedisease.com/US/patients/safety.html#gamma
About New York-Presbyterian Hospital/Weill Cornell Medical Center
New York-Presbyterian Hospital/Weill Cornell Medical Center, located in
New York City, is one of the leading academic medical centers in the world,
comprising the teaching hospital New York-Presbyterian and Weill Cornell
Medical College, the medical school of Cornell University. New York-
Presbyterian/Weill Cornell provides state-of-the-art inpatient, ambulatory and
preventive care in all areas of medicine, and is committed to excellence in
patient care, education, research and community service. Weill Cornell
physician-scientists have been responsible for many medical advances -- from
the development of the Pap test for cervical cancer to the synthesis of
penicillin, the first successful embryo-biopsy pregnancy and birth in the
U.S., the first clinical trial for gene therapy for Parkinson's disease, the
first indication of bone marrow's critical role in tumor growth, and, most
recently, the world's first successful use of deep brain stimulation to treat
a minimally-conscious brain-injured patient. New York-Presbyterian, which is
ranked sixth on the U.S. News & World Report list of top hospitals, also
comprises New York-Presbyterian Hospital/Columbia University Medical Center,
Morgan Stanley Children's Hospital of New York-Presbyterian, New York-
Presbyterian Hospital/Westchester Division and New York-Presbyterian
Hospital/The Allen Pavilion. Weill Cornell Medical College is the first U.S.
medical college to offer a medical degree overseas and maintains a strong
global presence in Austria, Brazil, Haiti, Tanzania, Turkey and Qatar. For
more information, visit http://www.nyp.org and http://www.med.cornell.edu.
About Baxter
Baxter International Inc., through its subsidiaries, assists healthcare
professionals and their patients with treatment of complex medical conditions,
including hemophilia, immune disorders, cancer, infectious diseases, kidney
disease, trauma and other indications. The company applies its expertise in
medical devices, pharmaceuticals and biotechnology to make a meaningful
difference in patients' lives.
This release includes forward-looking statements concerning GAMMAGARD S/D
and GAMMAGARD LIQUID [Immune Globulin Intravenous (IGIV)] relating to clinical
trials as well as potential future uses of the products. The statements are
based on assumptions about many important factors, including the following,
which could cause actual results to differ materially from those in the
forward-looking statements: continued review of Phase II data and the limited
number of patients studied to date; additional regulatory and other steps
required prior to the initiation of the larger Phase III study described in
the release; and other risks identified in Baxter's most recent filing on Form
10-K and other Securities and Exchange Commission filings, all of which are
available on Baxter's website. Baxter does not undertake to update its
forward-looking statements.
SOURCE Baxter International Inc.

Media: Chris Bona, +1-847-948-2815, Laura Grossman, +1-847-948-3026, or
Investors: Mary Kay Ladone, +1-847-948-3371, Clare Trachtman, +1-847-948-3085,
all of Baxter International Inc.