GE Healthcare announced today that results from its multicenter phase 2 study of flutemetamol were published in the September issue of Annals of Neurology. Flutemetamol is an investigational positron emission tomography (PET) imaging agent being developed by GE Healthcare, in the field of brain imaging.
The purpose of the phase 2 study was to investigate the efficacy of flutemetamol in differentiating between patients with clinically probable Alzheimer's disease (AD) and cognitively intact healthy volunteers (HVs). The primary endpoint was the efficacy of blinded assessments of flutemetamol binding to Beta-amyloid, the major constituent of amyloid plaque, which is a pathological hallmark of AD. In the study, subjects with a high probability of amyloid (27 AD patients) and a low probability of amyloid (25 healthy subjects) underwent PET imaging with flutemetamol. Five independent image readers, each blinded to the subject's clinical status, separately decided if each subject's image corresponded to normal or raised amyloid levels. The accuracy of image assessments was determined by comparing them to the subjects' clinical diagnoses. In addition, 20 subjects with a memory disorder known as mild cognitive impairment (MCI), which may represent a pre-dementia stage of AD, were enrolled and imaged with flutemetamol.
The image readers found that scans from 25 of the 27 AD patients displayed elevated flutemetamol uptake, as did 1 of 15 HVs who were older than 55 years, corresponding to a sensitivity of 93.1% and a specificity of 93.3% against their clinical diagnoses. In the group with MCI, visual inspection revealed raised binding of flutemetamol in 9 of 20 subjects. Test-retest reliability was very high when subjects underwent repeat scanning after 7 days. Additionally, comparable uptake ratios were seen when compared to 11CPIB of which flutemetamol is an analog.
"These data show that flutemetamol exhibits equivalent brain uptake to that of its parent molecule, 11C-Pittsburgh compound B, while also providing high test-retest replicability and potentially greater accessibility for clinical and research use," said Rik Vandenberghe, MD, PhD, Neurology Department, University Hospitals Leuven, Belgium.
"The importance of this study is underscored by the fact that it represents the first direct comparison of 11C-Pittsburgh compound B (which is also known as PiB) to a true analog of this compound," commented William E. Klunk, MD, PhD, professor of Psychiatry and Neurology at the University of Pittsburgh. The current study shows that, in addition to providing equivalent efficacy, flutemetamol actually offers greater test-retest reliability than has been reported with PiB. Flutemetamol thus appears to be a viable and practical alternative to PiB."
The study was also the subject of Dr. Bill Jagust's editorial in the same issue of the Annals of Neurology, which provides further analysis of the study.
The ongoing flutemetamol phase 3 trial program is a series of multicenter studies that include patients who consent to brain biopsy or to post-mortem assays to determine the level of association between imaging detection of amyloid and histopathology findings. A separate study is underway in patients with MCI who may progress to AD. The trials have already commenced with recruitment and imaging of patients at multiple sites in the USA and Europe.
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