Following my live tweets from the AACR molecular diagnostics and cancer therapeutics meeting here in Denver this week, some interesting offline discussions continued. A big focus here was on biomarkers and systems biology. Several readers observed that oncology seems to be ahead compared to other therapy areas.
What is interesting though, is that while oncology is heavy on science, pathways, targeted therapies and multiple mechanisms of actions, it is surprisingly low on predictive biomarkers. It does fare a little better on prognostic biomarkers, granted. In contrast, Alzheimer’s Disease (AD) in many ways, seems to be almost the opposite in that various biomarkers abound, but the field lags in effective targeted drugs and a deep understanding of the underlying biology (relative to oncology that is).
One area where we are likely to see more progress in the near future is in the use of imaging biomarkers for the diagnosis of early Alzheimer’s Disease.
Several companies are currently undertaking clinical trials with imaging biomarkers for AD including Bayer with florbetaben (BAY 94-9172), Avid Radiopharmaceuticals with AV-45 and GE Healthcare with flutemetamol. All three are in phase III development.
Currently the use of Pittsburgh compound B (PiB) in combination with PET allows the imaging of beta-amyloid plaques in the brain that are indicative of AD. However, there are limitations with the use of PiB since it requires use of an on-site cyclotron.
A recent paper by Rik Vandenberghe from the Catholic University Leuven, published in the September edition of the Annals of Neurology caught my attention on this topic. It reported phase 2 trial results from the use of 18F flutemetamol imaging in AD.
In this clinical trial, sponsored by GE Healthcare, blinded visual assessments of 18F- flutemetamol scans were undertaken in 27 subjects with probable early-stage AD and mild cognitive impairment (MCI). The results showed a sensitivity of 93.1% in the ability of the scan to diagnose early AD, as compared to clinical diagnosis as the Standard of Truth (25 out of 27 patients). 18F-flutemetamol was also shown in 20 subjects to have comparable regional standardized uptake value ratios (SUVRs) when compared to 11C-Pittsburgh compound B (11C-PiB). Correlation coefficients ranged from 0.89 to 0.92.
What makes the use of the 18F-labeled PiB derivative interesting is that 18F-flutemamol does not require the use of an on-site cyclotron, unlike 11C-PiB. As the study reports this may make it easier to access PET technology for clinical trials and research into AD.
GE Healthcare have already started a phase 3 trial program with flutemetamol, so it will be interesting to see whether the promising phase 2 results are confirmed when the phase 3 data is available after the study is completed later this year.
Data from other phase III clinical trials make this an area to watch out for. Hopefully the development of imaging biomarkers that allow for early diagnosis, will insoire both more basic research into the underlying biological mechanisms and also stimulate companies develop more targeted drugs for the treatment of what is essentially a horrible, progressive disease.
Photo Credit: Avid Radiopharmaceuticals
Top: Elderly Patient Control
Bottom: 18F AV-45 imaging of amyloid plaque in a patient with Alzheimer’s disease
Vandenberghe, R., Van Laere, K., Ivanoiu, A., Salmon, E., Bastin, C., Triau, E., Hasselbalch, S., Law, I., Andersen, A., Korner, A., Minthon, L., Garraux, G., Nelissen, N., Bormans, G., Buckley, C., Owenius, R., Thurfjell, L., Farrar, G., & Brooks, D. (2010). 18F-flutemetamol amyloid imaging in Alzheimer disease and mild cognitive impairment: A phase 2 trial Annals of Neurology, 68 (3), 319-329 DOI: 10.1002/ana.22068