AMYVID IS RELIABLE1

Amyvid has been shown to be reliable for estimating beta-amyloid neuritic plaque density.

Amyvid and autopsy results agree1,2*

STATISTICALLY SIGNIFICANT CORRELATION between Amyvid PET scan images and amyloid plaque deposition seen at autopsy (r=0.78; 95% CI:0.58 to 0.89; P<0.0001) (n=29)1

NEGATIVE AMYVID PET SCAN


Low Amyvid uptake in cortical gray matter1

PATHOLOGY RESULTS (IMMUNOHISTOCHEMISTRY)


No evidence of amyloid plaques1

POSITIVE AMYVID PET SCAN


High Amyvid uptake in cortical gray matter1

PATHOLOGY RESULTS (IMMUNOHISTOCHEMISTRY)


High levels of amyloid plaques1

Study 1: Assessed the correlation between amyloid plaques seen at autopsy and estimates for amyloid plaque density using Amyvid PET imaging1

DESIGN
  • 3 readers
  • Semiquantitative reading methodology (not intended for clinical use)
POPULATION
  • 35 terminally ill patients who received premortem Amyvid scans and then underwent autopsy (29 of which comprised the primary analysis set)

*Patient scans and corresponding autopsy slides are from the same patient.1

SELECT IMPORTANT SAFETY INFORMATION:
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

AMYVID IS ACCURATE1,3

Amyvid has been shown to be accurate for estimating beta-amyloid neuritic plaque density.

Objective evidence of amyloid pathology1*


SENSITIVITY
(95% CI: 80% to 100%)


SPECIFICITY
(95% CI: 78% to 100%)

Based on patients who died within 1 year of Amyvid scanning (n=46). With the entire data set of 59 patients who died within 2 years of Amyvid scanning, sensitivity was 92% (95% CI: 78% to 98%) and specificity was 100% (95% CI: 80% to 100%).

Study 2: Assessed the sensitivity and specificity of a binary visual read methodology in patients who underwent autopsy (truth standard).1

DESIGN
  • 5 readers (trained in person)
  • Binary visual read methodology
POPULATION
  • 59 terminally ill patients who received premortem Amyvid scans and then underwent autopsy to establish a truth standard.

*In patients with autopsies performed within 1 year of Amyvid scan (n=46). Sensitivity and specificity were calculated using the majority interpretation of the readers for the presence or absence of moderate to frequent amyloid plaques.

Twenty-nine (29) patients had an AD clinical diagnosis, 13 had another type of dementing disorder, 12 had no history of cognitive impairment, and 5 had MCI.

  • In those who had autopsy within 1 year of PET imaging (n=46), 28 had moderate-to-frequent plaques and 18 had no or sparse neuritic plaques at autopsy
    • Majority of readers rated Amyvid PET scans as positive in 27 of the 28 individuals (1 false positive), giving a sensitivity of 96% (95% CI: 80% to 100%)
    • Majority of readers rated Amyvid PET scans as negative in all 18 individuals (0 false negative) which corresponded to a specificity of 100% (95% CI: 78% to 100%)

SELECT IMPORTANT SAFETY INFORMATION:
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

AMYVID IS REPRODUCIBLE1

Amyvid has been shown to have high inter-reader reproducibility for estimating beta-amyloid neuritic plaque density1

High inter-reader reproducibility1

OF INTERPRETATIONS AGREED
with the majority
(95% CI:89.8% to 94.1%)(n=59)4

Overall Fleiss' kappa* statistic of 0.83 [95% CI: 0.78 to 0.88] [n=151];
the lower bound of the 95% CI exceeded the prespecified success criterion1

Study 2: Assessed the sensitivity and specificity of a binary visual read methodology in patients who underwent autopsy (truth standard)1

DESIGN
  • 5 readers (trained in person)
  • Binary visual read methodology
POPULATION
  • 59 terminally ill patients who received premortem Amyvid scans and then underwent autopsy to establish a truth standard

Study 3: Assessed the inter- and intra-reader image interpretation reproducibility in subjects with and without autopsy (truth standard)1

DESIGN
  • 5 readers (trained using electronic media)
  • Binary visual read methodology
POPULATION
  • 92 subjects who did not undergo autopsy (truth standard) in addition to 59 patients (same population from Study 2) with autopsy data
  • 33 randomly selected images were used to assess intra-reader reproducibility

“In conjunction with clinical assessment, Amyvid offers objective evidence to help you make a more informed diagnosis for patients like me, with signs and symptoms of cognitive decline.

AD=Alzheimer's disease; MCI=mild cognitive impairment.

*Fleiss' kappa: the degree of agreement among multiple readers over that which would be expected by chance.
Twenty-nine (29) patients had an AD clinical diagnosis, 13 had another type of dementing disorder, 12 had no history of cognitive impairment, and 5 had MCI.
Twenty (20) healthy volunteers, 52 patients.

SELECT IMPORTANT SAFETY INFORMATION:
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%)

References

  1. Amyvid [Prescribing Information]. Indianapolis, IN: Lilly USA, LLC.
  2. Data on File, Lilly USA, LLC, DOF-AM-US-0006.
  3. Clark CM, Pontecorvo MJ, Beach TG, et al; for the AV-A16 Study Group. Cerebral PET with florbetapir compared with neuropathology at autopsy for detection of neuritic amyloid-β plaques: A prospective cohort study. Lancet Neurol. 2012;11(8):669-678.
  4. Data on File, Lilly USA, LLC, DOF-AM-US-0005.

INDICATION

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.

Amyvid for intravenous use is supplied in multidose vials containing 500-1900 MBq/mL Florbetapir F 18.

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

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%)

Please see full Prescribing Information for Amyvid.

AM HCP ISI 10JAN2014