The founding executive director and chief science officer of the Alzheimer’s Drug Discovery Foundation discussed the recent approval of the imaging agent flortaucipir F18.
Howard Fillit, MD
At the end of May, the FDA gave the go-ahead to the intravenous imaging agent flortaucipir F18 (Tauvid; Avid Radiopharmaceuticals) for the imaging of tau pathology with positron emission tomography (PET) in the brains of adult patients with cognitive impairment who are being evaluated for Alzheimer disease.1
The safety and effectiveness of the imaging agent were evaluated in a pair of clinical studies, in which each had 5 evaluators read and interpret the imaging in more than 300 patients, including those with a terminal illness who agreed to participate in a postmortem brain donation program, as well as those with mild cognitive impairment (MCI). Those findings suggested that the tau tracer can support a pathological diagnosis of Alzheimer disease by identifying the underlying presence of NFTs at the B3 level (Braak stages V to VI) and high levels of Alzheimer disease neuropathologic change (ADNC) per National Institute on Aging—Alzheimer Association (NIA–AA) criteria.2,3
To glean some perspective for the clinical community, NeurologyLive spoke to Howard Fillit, MD, founding executive director and chief science officer, Alzheimer’s Drug Discovery Foundation (ADDF).
Howard Fillit, MD: In the long term, the approval of the first tau PET tracer will be important in providing earlier and more accurate Alzheimer diagnosis and can impact how providers, patients and caregivers approach present and future care. However, in the near future, the impact in clinical care may be limited at first; we will have to wait to see about how reimbursement affects the clinical implementation of the tau scan and what the market rollout might be. It is more likely the tau scan will have much greater value in clinical trials at this time (as an inclusion criterion, and for monitoring progression and the impact of therapy, as an outcome measure).
While this is the first PET tau scan approved for use, PET amyloid scans have been available since Amyvid, which was developed with funding support from the ADDF and approved in 2012. Together, these PET brain scans will give physicians meaningful information about the presence of both pathologies to help them validate an Alzheimer diagnosis in their patients. Another way these scans will be used in tandem is in some clinical trial studies, especially those with anti-amyloid approaches.
It may greatly accelerate the development of anti-tau therapies, especially in Alzheimer disease. The advantage of the PET scan, compared to a fluid biomarker, is that it can provide information about where pathological tau is physically located in the brain. This information has the potential to provide insight into the effects of a therapeutic intervention by clarifying the spatial relationship between tau and other pathologies such as amyloid measured by PET or atrophy measured by MRI in a clinical trial.
The ADDF’s Diagnostics Accelerator supports the development of additional reliable and affordable biomarker tests for Alzheimer’s. This unique program challenges the research community to develop cutting-edge biomarkers and explore novel diagnostic technologies. Research funded to date focuses on several methods and targets including blood tests in various stages of development, as well as eye scans and digital tools that can join PET scans in our diagnostics arsenal. The next step is the development and commercialization of blood tests for beta-amyloid and tau, which I believe will be on the market in the next two to three years.
Transcript edited for clarity.
1. FDA Approves First Drug to Image Tau Pathology in Patients Being Evaluated for Alzheimer’s Disease. News release. FDA; May 28, 2020. Accessed May 28, 2020. https://www.fda.gov/news-events/press-announcements/fda-approves-first-drug-image-tau-pathology-patients-being-evaluated-alzheimers-disease
2. Clark CM﻿, Pontecorvo MJ﻿, Beach TG﻿, et al; AV-45-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. doi:10.1016/S1474-4422(12)70142-4
3. Fleisher AS, Pontecorvo MJ, Devous Sr MD, et al. Positron Emission Tomography Imaging With [18F]flortaucipir and Postmortem Assessment of Alzheimer Disease Neuropathologic Changes. JAMA Neurol. Published online April 27, 2020. doi:10.1001/jamaneurol.2020.0528