INDIANAPOLIS, July 22, 2015 /PRNewswire/ -- Eli Lilly and
Company (NYSE: LLY) and Avid Radiopharmaceuticals, Inc., a wholly
owned subsidiary of Lilly, today announced new data showing that
knowledge of amyloid status as determined by Florbetapir F 18
Injection imaging altered diagnosis and management in the majority
of patients being studied. This is the first study to look at the
impact of amyloid imaging on diagnosis and actual patient
management using a randomized, controlled prospective
design.1 These findings were presented today at the
Alzheimer's Association International Conference® 2015
(AAIC®) in Washington,
D.C.
The presence of beta-amyloid neuritic plaque in the brain may
provide additional information to supplement a physician's clinical
assessment of a patient with cognitive impairment. However, a
negative beta-amyloid imaging scan indicates sparse to no plaques
are currently present, which is inconsistent with a
neuropathological diagnosis of Alzheimer's disease and reduces the
likelihood that a patient's cognitive impairment is due to the
disease.2 It is important to note that errors
may occur during image interpretation. Also, a positive scan does
not establish a diagnosis of Alzheimer's disease or other cognitive
disorders and a negative scan does not preclude the development of
brain amyloid in the future.
"These study results are the first to suggest in a controlled
study that adding florbetapir to the diagnostic evaluation changed
actual patient diagnosis and management by physicians who regularly
manage this complicated and devastating disease," said Michael Pontecorvo, Ph.D., vice president,
clinical development, Avid Radiopharmaceuticals, a wholly owned
subsidiary of Lilly. "Alzheimer's disease is one of many possible
causes of cognitive impairment, which can make diagnosis
challenging. These findings provide further support for how
knowledge of the presence or absence of amyloid pathology may
affect both diagnosis and management in patients being evaluated
for Alzheimer's disease or other possible causes of cognitive
decline."
In addition to altering patient diagnosis, results showed that
knowledge of amyloid status as determined by florbetapir imaging
changed patient management in the majority of study patients,
particularly Alzheimer's disease medications (cholinesterase
inhibitor use), in a direction consistent with amyloid status. The
researchers found no group differences in cognitive performance or
health outcomes at one year, and changes in medical history,
psychotropic drug use, and psychiatric-related events were not
significantly different between the immediate and delayed feedback
groups. There was no evidence of increased safety risk associated
with early disclosure of amyloid status.1
These data add to a growing body of work that suggests knowledge
of amyloid status may change intended and actual patient
management.3,4,5
Study Methods1
The goal of this multicenter
study was to evaluate the impact of amyloid positron emission
tomography (PET) on patient management and outcomes in a
randomized, controlled setting. After identifying patients seeking
diagnosis for mild impairment or dementia, where Alzheimer's
disease was considered a possible cause (<85 percent certain),
physicians recorded a working diagnosis and management plan.
Patients underwent a florbetapir PET scan and were then randomized
to either immediate or delayed (one year) feedback groups regarding
amyloid status.
When patients returned to the center after three months, the
physician updated the diagnosis and recorded an actual management
summary. Patients then returned to the center one year post
baseline for assessment of patient and caregiver outcomes including
change in cognitive status (ADAS-Cog), health outcomes/resource
utilization, mood, function and quality of life. The pre-specified
primary analyses examined the impact of immediate feedback versus
delayed feedback of amyloid status on diagnosis and management
changes at three months.
A total of 618 subjects were randomized to the immediate (308)
or to the delayed (310) amyloid PET feedback arms, including 174
subjects in France, 221 in
Italy and 223 in the United States. Six hundred and two
subjects completed the three month and 560 completed the one year
follow-up visits.
Key Results Details1
- The percentage of patients with management changes was higher
in the immediate feedback group compared to the delayed feedback
group (68.0 percent versus 56.0 percent)
- This difference was driven mainly by Alzheimer's disease
medication changes, particularly cholinesterase inhibitor use, when
patients were sorted by amyloid status
- In the immediate feedback group, cholinesterase inhibitor use
increased in amyloid positive subjects and decreased in amyloid
negative subjects so that 67.0 percent of amyloid positive versus
only 27.0 percent of amyloid negative subjects were receiving
medications three months after scan
- In contrast, in the delayed feedback group, Alzheimer's disease
medication use increased regardless of amyloid status such that
56.0 percent amyloid positive and 43.0 percent amyloid negative
subjects were receiving cholinesterase inhibitors
- Results suggested that knowledge of amyloid status as
determined by florbetapir imaging changed actual patient diagnosis
(32.6 percent in the immediate feedback group compared to 6.4
percent in the delayed feedback group)
- Of note, diagnosis change among cases with contradicting
initial diagnosis versus scan results was 85.6 percent for the
immediate feedback group compared to 11.9 percent for the delayed
feedback group
- There were no group differences in cognitive performance or
health outcomes at one year as measured by the following:
- Cognitive change from baseline (ADAS, MMSE, FAQ)
- Resource use on the RUD
- Quality of life on the QoL AD
- Caregiver Self Efficacy
Study limitations included:
- Physicians frequently failed to perform the diagnostic and
neuropsychology tests and follow-up visits that were a part of
their pre-scan management plan
- The study was not designed to assess health outcomes
impact
- The trial reflects current physician behavior and available
treatments. Results could change with physician education and
experience with amyloid PET scans, and with the advent of new
medications
About Amyvid™ (Florbetapir F 18
Injection)2
Amyvid is a radioactive diagnostic
agent for Positron Emission Tomography (PET) imaging of the brain
to estimate beta-amyloid neuritic plaque density in adult patients
with cognitive impairment who are being evaluated for Alzheimer's
Disease (AD) and other causes of cognitive decline.
A negative Amyvid scan indicates sparse to no neuritic plaques
and is inconsistent with a neuropathological diagnosis of AD at the
time of image acquisition; a negative scan result reduces the
likelihood that a patient's cognitive impairment is due to AD. A
positive Amyvid scan indicates moderate to frequent amyloid
neuritic plaques; neuropathological examination has shown this
amount of amyloid neuritic plaque is present in patients with AD,
but may also be present in patients with other types of neurologic
conditions as well as older people with normal cognition. Amyvid is
an adjunct to other diagnostic evaluations.
Limitations of Use:
- A positive Amyvid scan does not establish a diagnosis of AD or
other cognitive disorder
- Safety and effectiveness of Amyvid have not been established
for:
– Predicting development of dementia or
other neurologic condition
– Monitoring responses to therapies
Amyvid for intravenous use is supplied in 10 mL, 30 mL, or 50 mL
multidose vials containing 500-1900 MBq/mL Florbetapir F 18
WARNINGS AND PRECAUTIONS
Risk for Image Misinterpretation and Other Errors
- Errors may occur in the Amyvid estimation of brain neuritic
plaque density during image interpretation
- Image interpretation should be performed independently of the
patient's clinical information. The use of clinical information in
the interpretation of Amyvid images has not been evaluated and may
lead to errors. Other errors may be due to extensive brain atrophy
that limits the ability to distinguish gray and white matter on the
Amyvid scan as well as motion artifacts that distort the image
- Amyvid scan results are indicative of the brain neuritic
amyloid plaque content only at the time of image acquisition and a
negative scan result does not preclude the development of brain
amyloid in the future
Radiation Risk
- Amyvid, similar to other radiopharmaceuticals, contributes to a
patient's overall long-term cumulative radiation exposure.
Long-term cumulative radiation exposure is associated with an
increased risk of cancer. Ensure safe handling to protect patients
and health care workers from unintentional radiation exposure
MOST COMMON ADVERSE REACTIONS
- The most common adverse reactions reported in clinical trials
were headache (1.8%), musculoskeletal pain (0.7%), blood pressure
increased (0.7%), nausea (0.7%), fatigue (0.5%), and injection site
reaction (0.5%)
For more information about florbetapir F 18, please see the
Prescribing Information at
http://pi.lilly.com/us/amyvid-uspi.pdf.
AM HCP ISI 10JAN2014
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
©Lilly USA, LLC 2015. All
rights reserved.
Amyvid™ is a trademark of Eli Lilly and Company.
Lilly Forward-Looking Statement
This press release contains certain forward-looking statements
about florbetapir F 18, a radioactive diagnostic agent indicated
for brain imaging of beta-amyloid plaques in patients with
cognitive impairment who are being evaluated for Alzheimer's
Disease and other causes of cognitive decline. This release
reflects Lilly's current beliefs; however, as with any
pharmaceutical product, there are substantial risks and
uncertainties in the process of development and commercialization.
There is no guarantee that future study results and patient
experience will be consistent with study findings to date or that
florbetapir F 18 will be commercially successful. For further
discussion of these and other risks and uncertainties, see Lilly's
filings with the United States Securities and Exchange Commission.
Lilly undertakes no duty to update forward-looking statements.
1 Pontecorvo M, Siderowf A, Mintun M, et al. A
randomized, controlled, multicenter, international study of the
impact of florbetapir (18F) PET amyloid imaging on
patient management and outcome. Presented at The Alzheimer's
Association International Conference (AAIC) 2015, July 18-23, 2015; Washington, D.C.
2 Amyvid [package insert]. Indianapolis, IN: Lilly USA, LLC; 2012.
3 Grundmann, et al. 2013: 31% change in AD drug therapy
and 7% change in non AD drug therapy in 229 patients (intended
mgmt.).
4 Sanchez-Juan et al. 2014: 35% change in cholinesterase
inhibitor or memantine use in 140 patients
5 Zwan et al. 2014 (abstract) 80 patient study found 20%
change in diagnosis and 52% change in patient management
(diagnostic studies, drug therapy, and other)
Refer to: Nicole Hebert;
hebert_nicole@lilly.com; 317.701.9984 (Lilly)
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