INDIANAPOLIS, Dec. 8, 2016 /PRNewswire/ -- Eli Lilly and
Company (NYSE:LLY) today presented detailed results of its phase 3
EXPEDITION3 trial at the 9th Clinical Trials on
Alzheimer's Disease (CTAD) meeting. As previously disclosed,
solanezumab did not meet the primary endpoint in the EXPEDITION3
clinical trial, a study of solanezumab initiated in people with
mild dementia due to Alzheimer's disease (AD), and Lilly will not
pursue regulatory submissions for solanezumab for the treatment of
mild dementia due to AD.
"The results of EXPEDTION3 are without question disappointing,"
said Eric Siemers, M.D.,
distinguished medical fellow at Lilly. "However, Lilly remains
committed to finding solutions for this devastating disease. We
will continue to analyze study results and work with the external
scientific community in the hopes of uncovering findings that will
help shape and advance future Alzheimer's disease research."
Lawrence S. Honig, M.D., Ph.D.,
professor of neurology at Columbia
University Medical Center and principal investigator of the
EXPEDITION3 study, presented the data at the meeting.
"Alzheimer's is a challenging disease that researchers have been
committed to studying for some years," Dr. Honig said. "Now is not
the time to give up. While the outcome of this study is not what we
had hoped for, it is reasonable to believe that disease modifying
therapies to slow down the progression of Alzheimer's disease will
be discovered."
A Summary of Key Results
While the study results,
including many secondary clinical endpoints, directionally favored
solanezumab, the magnitudes of treatment differences were
small.
Primary Endpoint
- Patients treated with solanezumab did not experience a
statistically significant slowing in cognitive decline compared to
patients treated with placebo. This finding represented an 11
percent reduction in decline (p=.095), as measured by the
Alzheimer's Disease Assessment Scale-Cognitive
(ADAS-Cog14) subscale. The ADAS-Cog14
measures a person's cognitive functions, including memory,
attention and language abilities.1
Key Secondary Clinical Endpoints
As the primary
endpoint was not met in this study, the p-values for the efficacy
secondary statistical analyses were not adjusted for multiple
comparisons.
- Patients treated with solanezumab had a 13 percent slowing of
cognitive decline (p=0.014) compared to patients treated with
placebo as measured by the Mini-Mental State Examination (MMSE).
The MMSE is the most commonly used test for complaints of problems
with memory or other mental abilities and can be used by clinicians
to help diagnose dementia and to help assess its progression and
severity. It consists of a series of questions and tests, each of
which scores points if answered correctly. The MMSE tests a number
of different mental abilities, including a person's memory,
attention and language.2
- The Clinical Dementia Rating-Sum of Boxes (CDR-SB) scale showed
a 15 percent slowing in decline (p=0.004) between patients treated
with solanezumab and patients treated with placebo. The CDR-SB
scale measures cognitive and functional performance — in areas such
as memory, orientation and personal care — through semi-structured
interviews of patients and their family members or other reliable
informants.3
- Patients treated with solanezumab had a slowing of decline in
complex activities of daily living compared to patients treated
with placebo. This finding represented a 14 percent slowing of
decline (p=.019) as measured by the Alzheimer's Disease Cooperative
Study-Instrumental Activities of Daily Living (ADCS-iADL). The
ADCS-iADL scale measures a person's independent performance in
complex activities of daily living such as participating in a
conversation, preparing a meal or shopping.4
- A different functional measure, the FAQ (Functional Activities
Questionnaire), did not show a statistically significant difference
between patients treated with solanezumab and patients treated with
placebo (7 percent reduction in decline, p=0.140). The FAQ scale is
a different informant-based measure of functional abilities.
Informants provide performance ratings of the patient on ten
complex higher-order activities.5
Biomarkers
Changes in plasma a-beta were similar to those seen in previous
studies, and the differences between treatment and placebo groups
were statistically significant. Changes in amyloid deposition as
measured by positron emission tomography (PET) imaging did not
reach statistical significance between treatment and placebo
groups.
Adverse events
- Events more frequent in the solanezumab treatment group that
were statistically significant include: spinal osteoarthritis (1.1
percent in the solanezumab group, 0.4 percent in the placebo
group), dysuria (0.9 percent in the solanezumab group, 0.2 percent
in the placebo group), vitamin D deficiency (1.4 percent in the
solanezumab group, 0.6 percent in the placebo group), and nasal
congestion (1.2 percent in the solanezumab group, 0.4 percent in
the placebo group).
- The incidence of vasogenic edema (ARIA-E or amyloid-related
imaging abnormality–edema/effusions) was approximately 0.1 percent
of patients treated with solanezumab and 0.3 percent of patients on
placebo.
About Solanezumab
Solanezumab is Lilly's phase 3 monoclonal antibody being studied
as a potential therapy for people with mild cognitive impairment
due to Alzheimer's disease (EXPEDITION-PRO), preclinical
Alzheimer's disease (Anti-Amyloid Treatment in Asymptomatic
Alzheimer's "A4"), and Dominantly Inherited Alzheimer's Disease
("DIAN").
About EXPEDITION3
EXPEDITION3 is a multinational, phase 3 trial of solanezumab in
more than 2,100 patients diagnosed with mild dementia due to
Alzheimer's disease. The study includes an 18-month
placebo-controlled period followed by an open label extension.
Enrollment was completed in 2015 and the last patient visit for the
placebo-controlled period occurred in October 2016. EXPEDITION3 is the first phase 3
trial to evaluate only people with mild dementia due to Alzheimer's
disease.
About Alzheimer's Disease
Alzheimer's disease is a fatal illness that is believed to start
with changes in the brain that may begin 20 years or more before
symptoms appear.[6] Those changes cause a progressive decline in
memory and other aspects of cognition that eventually lead to
dementia.
Dementia due to Alzheimer's disease is the most common form of
dementia, accounting for 60 to 80 percent of dementia
cases.6 There are currently an estimated 47 million
people living with dementia worldwide.7 The number of
people affected by dementia is expected to be nearly 75 million in
2030 and 131 million in 2050.7 Estimates vary, but
experts suggest that as many as 5.4 million Americans may have
Alzheimer's disease.6
About Eli Lilly and Company
Lilly is a global
healthcare leader that unites caring with discovery to make life
better for people around the world. We were founded more than a
century ago by a man committed to creating high-quality medicines
that meet real needs, and today we remain true to that mission in
all our work. Across the globe, Lilly employees work to discover
and bring life-changing medicines to those who need them, improve
the understanding and management of disease, and give back to
communities through philanthropy and volunteerism. To learn more
about Lilly, please visit us at www.lilly.com and
newsroom.lilly.com/social-channels. P-LLY
This press release contains certain forward-looking statements
about solanezumab, an anti-amyloid monoclonal antibody in clinical
testing for treatment of Alzheimer's disease, and reflects Lilly's
current beliefs. However, as with any pharmaceutical product, there
are substantial risks and uncertainties in the process of
development and commercialization. Among other things, there is no
guarantee that future study results and patient experience will be
consistent with study findings to date or that solanezumab will
receive regulatory approvals or be commercially successful. For
further discussion of these and other risks and uncertainties, see
Lilly's most recent Form 10-K and Form 10-Q filings with the United
States Securities and Exchange Commission. Except as required by
law, Lilly undertakes no duty to update forward-looking statements
to reflect events after the date of this release.
1 Liu-Seifert H., et
al. Cognitive and Functional Decline and Their Relationship in
Patients with Mild Alzheimer's Dementia. Journal of Alzheimer's
Disease. 43 (2015) 949–955
2 Alzheimer's Society. The Mini Mental State
Examination.
https://www.alzheimers.org.uk/site/scripts/documents_info.php?documentID=121.
Accessed November 2016
3 The Washington University
Knight ADRC. http://alzheimer.wustl.edu/CDR/CDR.htm. Accessed
November 2016.
4 Liu-Seifert H., et al.
Cognitive and Functional Decline and Their Relationship in Patients
with Mild Alzheimer's Dementia. Journal of Alzheimer's
Disease. 43 (2015) 949–955
5 Alzheimer's Association. Tools for Early
Identification, Assessment, and Treatment for People with
Alzheimer's Disease and Dementia.
https://www.alz.org/national/documents/brochure_toolsforidassesstreat.pdf.
Accessed November 2016.
6 Alzheimer's Association. 2016 Alzheimer's Disease
Facts and Figures.
http://www.alz.org/documents_custom/2016-facts-and-figures.pdf.
Accessed November 2016.
7 Alzheimer's Disease International. Dementia
statistics. http://www.alz.co.uk/research/statistics. Accessed
November 2016.
Refer to: Media – Nicole Hebert; hebert_nicole@lilly.com;
317.701.9984
Investors – Phil Johnson;
johnson_philip_l@lilly.com; 317.655.6874
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