Vizamyl color images provided accurate
amyloid detection

In Study 1:

High median sensitivity and specificity in autopsy standard-of-truth assessment among five independent, blinded image readers. 1

In Study 2:

  • Vizamyl color image reads demonstrated high inter-reader agreement for visual image interpretation (kappa score 0.83, 95% CI [0.79-0.86]) 1
  • An intra-reader reproducibility analysis involving two readings for each of 29 duplicate patient images showed: One of the five readers had complete agreement for all 29 images, two readers had discordant reads for a single
    image, and two readers had discordant reads for two images 1
  • Intra-reader reproducibility for a subgroup of eight images from aMCI patients showed: All five readers had complete agreement for all
    duplicate images 1
aMCI, amnestic mild cognitive impairment.
INDICATIONS AND USAGE: Vizamyl is indicated for positron-emission tomography (PET) imaging of the brain to estimate β-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 scan indicates sparse to no neuritic plaques, inconsistent with a 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 scan indicates moderate to frequent amyloid neuritic plaques. This amount of amyloid neuritic plaque has been shown to be present in patients with AD but may also be present in patients with other neurologic conditions as well as in older people with normal cognition. Vizamyl is an adjunct to other diagnostic evaluations. Limitations: A positive scan does not establish a diagnosis of AD or other cognitive disorder. The safety and effectiveness of Vizamyl have not been established for predicting the development of dementia or other neurologic conditions or for monitoring responses to therapies. CONTRAINDICATIONS: Known hypersensitivity to Vizamyl or any excipient, including polysorbate 80. Image Misinterpretation: Errors may occur while interpreting Vizamyl PET images. Image interpretation is performed independently of the patient’s clinical information. The use of clinical information in the interpretation of Vizamyl images has not been evaluated and may lead to errors. Extensive brain atrophy may limit the ability to distinguish grey and white matter on a Vizamyl scan. Motion artifacts may distort the image. Images should be interpreted only by readers who have completed a reader training program available from GE Healthcare.

Median percent sensitivity and specificity results of images
with autopsy standard of truth for NDA clinical trials with Vizamyl (N=68) 1

Study 1 (In-person training) and Study 2 (Electronic media training)

Phase 3 study designs 1

STUDY 1: Autopsy standard-of-truth assessment

  • Of the 180 patients dosed with Vizamyl (176 imaged), 44 patients had no cognitive impairment, 135 had dementia, none had MCI, and one had memory loss of unspecified nature
  • 68 patients with Vizamyl positron-emission tomography (PET) images and postmortem cerebral cortical amyloid status
    (43 positive and 25 negative) were included in the primary analysis
  • Premortem PET images from terminally ill patients were evaluated and compared to postmortem (histopathological) standard-of-truth assessments of cerebral cortical neuritic plaque density in patients who died during the study

MCI, mild cognitive impairment.

STUDY 2: Assessment of electronic reader training program effectiveness

  • Evaluated PET images from a range of subjects with different cognitive abilities, who had participated in earlier NDA studies of Vizamyl
  • Analysis included images from 68 patients included in Study 1, with a postmortem (histopathological) amyloid neuritic plaque density standard of truth
  • Inter-reader reproducibility was assessed among the images from patients with a standard of truth (the 68 patients identified above and 36 patients with known or suspected NPH with in vivo biopsy), combined with images from 28 cognitively normal volunteers 55 years of age and older, 80 patients with aMCI, 33 patients with pAD, and 31 young, healthy volunteers
  • Intra-reader reproducibility was assessed from 29 images that were reread randomly
aMCI, amnestic mild cognitive impairment; pAD, probable AD; NPH, normal pressure hydrocephalus.

Safety of Vizamyl demonstrated in clinical trials

In clinical trials of 761 patients dosed, one subject experienced a serious hypersensitivity reaction. 1

  • This reaction was accompanied by flushing, dyspnea, and chest pressure
  • The reaction occurred within minutes of administration of Vizamyl, and the patient recovered with treatment

Adverse reactions reported in clinical trials (n=761)

vizamyl_adversereactions-chart

The most commonly reported adverse reactions occurred at a rate of ≤2% and were of mild to moderate intensity. 1

Radiation safety

  • The recommended dose is 185 MBq (5 mCi) injected intravenously 1
  • The adult effective dose is 5.92 mSv 1
    • 3.5 mSv average annual background exposure in United States
  • Concomitant use of CT scan will add radiation exposure (up to an average of 2.2 ± 1.3 mSv). Actual radiation dose is operator- and scanner-dependent

Additional Radiation Safety Information: As with all radiopharmaceutical agents, Vizamyl will contribute 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 healthcare workers from unintentional radiation exposure. Encourage patients to hydrate and void frequently before and for 24 hours following Vizamyl administration.

Important Risk and Safety Information About Vizamyl™ (Flutemetamol F 18 Injection)

INDICATIONS AND USAGE: Vizamyl is indicated for positron-emission tomography (PET) imaging of the brain to estimate β-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 scan indicates sparse to no neuritic plaques, inconsistent with a 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 scan indicates moderate to frequent amyloid neuritic plaques. This amount of amyloid neuritic plaque has been shown to be present in patients with AD but may also be present in patients with other neurologic conditions as well as in older people with normal cognition. Vizamyl is an adjunct to other diagnostic evaluations. Limitations: A positive scan does not establish a diagnosis of AD or other cognitive disorder. The safety and effectiveness of Vizamyl have not been established for predicting the development of dementia or other neurologic conditions or for monitoring responses to therapies. CONTRAINDICATIONS: Known hypersensitivity to Vizamyl or any excipient, including polysorbate 80. WARNINGS AND PRECAUTIONS — Hypersensitivity Reactions: Reactions such as flushing and dyspnea have been observed within minutes following administration and may occur in patients with no history of exposure to Vizamyl. Have resuscitation equipment and trained personnel available. Image Misinterpretation: Errors may occur while interpreting Vizamyl PET images. Image interpretation is performed independently of the patient’s clinical information. The use of clinical information in the interpretation of Vizamyl images has not been evaluated and may lead to errors. Extensive brain atrophy may limit the ability to distinguish grey and white matter on a Vizamyl scan. Motion artifacts may distort the image. Images should be interpreted only by readers who have completed a reader training program available from GE Healthcare. Radiation Risk: Like all radiopharmaceuticals, Vizamyl contributes to a patient’s long-term, cumulative radiation exposure and cancer risk. Ensure safe handling to protect patients and healthcare workers from unintentional radiation exposure. ADVERSE REACTIONS: The most commonly reported adverse reactions in NDA clinical trials were flushing, increased blood pressure, headache, nausea, and dizziness. DRUG INTERACTIONS: Drug-drug interaction studies have not been performed in patients to establish the extent, if any, to which concomitant medications may alter Vizamyl image results. SPECIFIC POPULATIONS — Pregnancy: It is not known whether Vizamyl can cause fetal harm when administered to a pregnant woman or if it can affect reproductive capacity. Radiopharmaceuticals, including Vizamyl, have the potential to cause fetal harm, the likelihood of which depends on the stage of fetal development and the magnitude of the radiopharmaceutical dose. Vizamyl should be given to a pregnant woman only if clearly needed. Nursing Mothers: It is not known whether flutemetamol is excreted in human milk. Because many drugs are excreted in human milk and there is a potential for radiation exposure to nursing infants, avoid use of Vizamyl in a breastfeeding mother or have the mother temporarily interrupt breastfeeding for 24 hours after exposure. Pediatric Use: Vizamyl is not indicated for use in pediatric patients. Geriatric Use: No overall differences in safety were observed between older and younger subjects. OVERDOSAGE: The clinical consequence of overdosing with Vizamyl has not been reported. It is unknown whether or not flutemetamol is dialyzable. In case of overdose of radioactivity, hydration and frequent urination should be encouraged.

Prior to Vizamyl administration, please read the Full Prescribing Information.

Reference: 1. Vizamyl [prescribing information]. Arlington Heights, IL: GE Healthcare; 2014.