Piramal Imaging has announced the publication of results from its pivotal Phase III trial of Neuraceq™ (florbetaben F18 injection), a radiopharmaceutical used with positron emission tomography (PET) imaging to estimate the density of neuritic beta-amyloid plaques in the brains of adult patients with cognitive impairment who are being evaluated for Alzheimer’s disease (AD) and other causes of cognitive decline. The results, which appear in the current issue of Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association, demonstrate the high diagnostic accuracy of Neuraceq scans, making it a valuable beta-amyloid targeting PET tracer in the clinic with great potential to serve as biomarker supporting clinical AD diagnosis.
The Phase III results led to the March 2014 U.S. Food and Drug Administration (FDA) approval of Neuraceq for PET imaging of the brain to estimate beta-amyloid neuritic plaque density in adult patients with cognitive impairment who are being evaluated for AD and other causes of cognitive decline. Neuraceq received marketing authorization from the European Commission in February 2014.
“Results from the phase III study validate an excellent consensus between the gold standard post-mortem pathology and florbetaben PET data, suggesting the very good suitability of florbetaben PET imaging for use in clinical practice,” said lead author Osama Sabri, MD, PhD, Department of Nuclear Medicine at the University of Leipzig, Germany. “The high sensitivity and specificity for florabetaben PET were confirmed by histopathology in clinically relevant whole-brain visual analyses, enabling the estimation of amyloid pathology. Together with results from earlier studies, these latest data support the value of florbetaben PET as a diagnostic marker and a valuable adjunct for the exclusion of Alzheimer’s disease or a differential diagnosis of dementia.”
The open-label, non-randomized, multicenter, Phase III trial was designed to demonstrate the accuracy of Neuraceq by comparing in vivo PET imaging with post-mortem histopathology. In this study, investigators analyzed brain images and tissue from 74 deceased subjects, out of 216 trial participants who underwent Neuraceq injection and PET imaging; the participants included 205 end-of-life patients who had agreed to participate in a post-mortem brain donation program. 1
The investigators also conducted a tissue-scan matched regional analysis on a subgroup. In total, 244 tissue-matched regions of interest (ROIs) were analyzed. A high correlation between florbetaben accumulation and presence of beta-amyloid plaques was found.1
The data have potentially important implications for the diagnosis of dementia, of which there are an estimated 7.7 million2 new cases each year worldwide. AD accounts for 60-80%3 of all dementia diagnoses. However, an estimated 20-30%4 of clinical diagnoses of probable AD are found to be incorrect upon post-mortem histological investigation, underscoring the need for more accurate diagnostic tools.
“Our phase III data demonstrate the accuracy and reliability of Neuraceq PET imaging in detecting beta-amyloid neuritic plaques in the brain, and supported the approvals of this radiotracer by regulatory bodies in the US and Europe,” noted Andrew Stephens, Chief Medical Officer, Piramal Imaging. “We hope these findings lead to more timely diagnosis and intervention in individuals with suspected Alzheimer’s disease and other forms of dementia, as well as to widespread reimbursement for the use of this innovative diagnostic tool.”
About Neuraceq™ (florbetaben F18 injection)
Neuraceq™ is indicated 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 Neuraceq™ scan indicates sparse to no amyloid 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 Neuraceq™ 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.
Neuraceq™ is an adjunct to other diagnostic evaluations.
Limitations of Use
A positive Neuraceq™ scan does not establish the diagnosis of AD or any other cognitive disorder.
- Safety and effectiveness of Neuraceq™ have not been established for:
- Predicting development of dementia or other neurologic conditions;
- Monitoring responses to therapies.
Important Safety Information
Risk for Image Interpretation and Other Errors
Neuraceq™ can be used to estimate the density of beta-amyloid neuritic plaque deposition in the brain. Neuraceq™ is an adjunct to other diagnostic evaluations. Neuraceq™ images should be interpreted independent of a patient’s clinical information. Physicians should receive training prior to interpretation of Neuraceq™ images. Following training, image reading errors (especially false positive) may still occur. Additional interpretation errors may occur due to, but not limited to, motion artifacts or extensive brain atrophy.
Administration of Neuraceq™, 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. It is important to ensure safe handling to protect patients and health care workers from unintentional radiation exposure.
Most Common Adverse Reactions
In clinical trials, the most frequently observed adverse drug reactions in 872 subjects with 978 Neuraceq™ administrations were injection/application site erythema (1.7%), injection site irritation (1.2%), and injection site pain (3.9%).