- Findings lead to decision to start Phase III pivotal study of
LY2062430 in 2009
Eli Lilly and Company (NYSE: LLY) today announced interim results
of its Phase II study of LY2062430, an investigational anti-amyloid
beta monoclonal antibody for the treatment of mild to moderate
Alzheimer's disease. In this study, intravenously administered
LY2062430 bound to the amyloid beta protein, resulting in increased
amounts of amyloid beta in participants' blood and cerebrospinal
fluid. These and other results suggest that by binding to soluble
amyloid beta proteins, LY2062430 may begin to dissolve the amyloid
plaques that are present in the brains of patients with Alzheimer's
disease. While the precise cause of Alzheimer's disease is not known,
it has been shown that people with this disorder have an excess of
amyloid beta plaque in the brain, particularly in the regions
associated with memory. It is theorized that decreasing the total
amount of amyloid plaque and other forms of the amyloid beta protein
in the brain may result in slowing of the disease progression.
Importantly, LY2062430 was well tolerated with no evidence of
treatment-related brain inflammation, bleeding or other side
effects. The findings from this Phase II study were presented today
at the Alzheimer's Association's 2008 International Conference on
Alzheimer's Disease (ICAD) in Chicago.
In this randomized, controlled trial, researchers evaluated the
safety and tolerability of LY2062430 administered intravenously in
patients with Alzheimer's disease and in healthy volunteers. They
assessed the effects of the antibody on levels of amyloid beta in the
blood and cerebrospinal fluid, as an indirect measure of the effect
of the antibody on amyloid beta present in the brain. Cerebrospinal
fluid, which surrounds the brain and spinal cord, is thought to
provide important biomarker data in addition to that obtained from
blood. Amyloid plaques, the pathological hallmark of Alzheimer's
disease, are composed largely of aggregated amyloid beta proteins.
Amyloid plaques or other types of the amyloid beta protein are
thought ultimately to disrupt normal nerve cell function in the
brain, leading to the dementia that characterizes Alzheimer's
"We are encouraged that in this study, we saw increased amyloid
beta which is thought to be bound to LY2062430, in both the blood and
cerebrospinal fluid. We hypothesize that this effect may lead to
reduced formation of amyloid plaques in the brain after long-term
treatment," said Eric Siemers, M.D., Medical Director, Alzheimer's
disease research for Eli Lilly and Company. "Alzheimer's disease is
complex, and there's a real need for new treatments that might be
shown ultimately to slow disease progression. In addition to the
biomarker results, we are particularly encouraged by the finding that
patients who received the monoclonal antibody treatment over 12 weeks
appeared to have no treatment-related side effects."
In this 12-week Phase II study, researchers gave 52 mild to
moderate Alzheimer's disease patients infusions of placebo or
LY2062430 in varying doses: 100mg or 400mg once a week, or 100mg or
400mg every four weeks. Alzheimer's disease symptom severity was also
evaluated. In addition, 16 volunteers each received a single dose of
100mg of LY2062430 or placebo. For all study participants, safety
assessments included magnetic resonance imaging (MRI) and
cerebrospinal fluid examinations. A sub-study of 24 patients and 13
volunteers underwent single photon emission tomography (SPECT)
scanning using an experimental tracer to assess levels of amyloid
beta plaque in the brain.
The interim analysis showed that weekly infusions of LY2062430 up
to 400mg per dose was well tolerated, with no side effects related to
treatment. An evaluation of MRI brain imaging and an assessment of
cerebrospinal fluid showed no evidence of brain inflammation or
bleeding. As expected for a study of this duration, no change in
patients' cognitive scores was observed and there was no change in
levels of brain amyloid beta plaque as measured by the SPECT tracer.
In addition to the increase in the two major forms of the amyloid
beta protein seen in blood and cerebrospinal fluid, an increase in
the two other types of the amyloid beta protein thought to be present
only in amyloid plaques was observed in participants' blood and
cerebrospinal fluid. The biomarker effects lasted for several weeks.
These biomarker findings suggest that longer term treatment with
LY2062430 may slow the clinical progression of Alzheimer's disease,
thus providing a rationale for additional trials of LY2062430.
"Results from this Phase II study are promising, and we are
pleased to announce our intention to commence a Phase III pivotal
study of LY2062430 beginning in 2009," said Steven M. Paul, M.D.,
Executive Vice President, Science and Technology, President of Lilly
Research Laboratories. "Additionally we are currently enrolling
patients into the Phase III study called IDENTITY, which examines
treatment with LY450139, an investigational gamma secretase inhibitor
believed to slow the rate of formation of amyloid beta, potentially
slowing disease progression. These two neuroscience pipeline
candidates represent potentially important advances in the effort to
slow the progression of this fatal disease, and demonstrate our
longstanding commitment to developing treatments for devastating
About Alzheimer's Disease
Alzheimer's disease is a progressive neurodegenerative condition
that is the most common cause of dementia in patients over 65 years
of age. Estimates show that 6-8 percent of people older than age 65
are affected by Alzheimer's disease(1), totaling approximately 5
million people in the United States alone(2). Every 72 seconds, an
American is developing Alzheimer's disease(3), and it is the
seventh-leading cause of death in the United States(4). The direct
and indirect health care costs associated with Alzheimer's disease in
the U.S. are estimated to be about US$150 billion(5). In 2005, the
total cost worldwide was estimated at US$315.4 billion(6).
Given the aging population, without the availability of medicines
that delay or prevent the onset of Alzheimer's disease, the number of
affected people worldwide is expected to quadruple by the year
2050(7). The average duration between onset of symptoms and death due
to complications of Alzheimer's disease is about 8-10 years(8). The
burden to caregivers and health care costs can increase dramatically
in the late stages of Alzheimer's disease, when patients cannot
maintain independent function and are frequently bedridden.
LY2062430 binds specifically to soluble amyloid beta and thereby
alters the sticky characteristics of this peptide. Alzheimer's
disease theory suggests that amyloid beta kills brain cells. Clinical
studies have examined the ability of LY2062430 to impact amyloid beta
in blood and cerebrospinal fluid and found significant dose-dependent
changes. To date, the most frequently occurring side effect
experienced in clinical studies with LY2062430 has been mild chills
consistent with an infusion reaction. For a more complete listing of
potential side effects, prospective clinical trial participants
should refer to the informed consent document.
Lilly, a leading innovation-driven corporation, is developing a
growing portfolio of first-in-class and best-in-class pharmaceutical
products by applying the latest research from its own worldwide
laboratories and from collaborations with eminent scientific
organizations. Headquartered in Indianapolis, Ind., Lilly provides
answers -- through medicines and information -- for some of the
world's most urgent medical needs. Additional information about Lilly
is available at www.lilly.com
This press release contains forward-looking statements about the
potential of the investigational compound LY2062430 and reflects
Lilly's current beliefs. However, as with any pharmaceutical product
under development, there are substantial risks and uncertainties in
the process of development and regulatory review. There is no
guarantee that the product will receive regulatory approvals, or that
the regulatory approval will be for the indication(s) anticipated by
the company. There is also no guarantee that the product will prove
to be commercially successful. For further discussion of these and
other risks and uncertainties, see Lilly's filing with the United
States Securities and Exchange Commission. Lilly undertakes no duty
to update forward-looking statements.
(1) Small, GW, Rabins, PV, Barry, PP, Buckholtz, NS, DeKosky, ST,
Ferris, SH, Finkel, SI, Gwyther, LP, Khachaturian, ZS, Lebowitz, BD,
McRae, TD, Morris, JC, Oakley, F, Schneider, LS, Streim, JE,
Sunderland, T, Teri, LA, Tune LE. Diagnosis and Treatment of
Alzheimer Disease and Related Disorders: Consensus Statement of the
American Association for Geriatric Psychiatry, the Alzheimer's
Association, and the American Geriatrics Society. JAMA 1997; 278:
(2) Alzheimer's Association. "2008 Alzheimer's Disease Facts and
Figures." Available at:
. Accessed July 1, 2008.
(3) American Public Health Association. "Mind Your Memory &
Alzheimer's Disease!" Available at: http://www.apha.org/membergroups/
newsletters/sectionnewsletters/public_edu/fa ll07/alzheimer.htm .
Accessed July 1, 2008.
(4) Centers for Disease Control and Prevention. "National Vital
Statistics Reports." Available at:
July 1, 2008.
(5) Alzheimer's Association. "2008 Alzheimer's Disease Facts and
Figures." Available at:
. Accessed July 1, 2008.
(6) Wimoa, Anders, Bengt Winblada, and Linus J. Jonssonb. An
estimate of the total worldwide societal costs of dementia in 2005.
Alzheimer's & Dementia (2007) 3: 81-91.
(7) Brookmeyer R, Johnson E, Ziegler-Graham K, Arrighi M.
Forecasting the Global Burden of Alzheimer's disease. Alzheimer's &
Dementia (2007) 3:186-191.
(8) National Institute on Aging. "Alzheimer's Disease Fact
Sheet." Available at
July 1, 2008.
Web site: http://www.lilly.com
ots Originaltext: Eli Lilly and Company
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