Findings lead to decision to start Phase III pivotal study of LY2062430
CHICAGO, July 30 /CNW/ -- 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 disease.
"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 brain illnesses."
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 $150 billion(5). In 2005, the total cost
worldwide was estimated at $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
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
(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:
l07/alzheimer.htm . Accessed July 1, 2008.
(4) Centers for Disease Control and Prevention. "National Vital
Statistics Reports." Available at:
http://www.cdc.gov/nchs/data/nvsr/nvsr55/nvsr55_19.pdf . Accessed July 1,
(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 http://www.nia.nih.gov/Alzheimers/Publications/adfact.htm .
Accessed July 1, 2008.
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