Labcorp Drug Development has continued to invest in the technology, innovation and expertise globally to support clients focused on bringing life-changing treatments to patients with neurological diseases. We recently spoke with Robert Martone, Associate Director, Neurology Biomarkers with the Biomarker Solution Center, to learn about the acceleration and expansion of biomarkers and diagnostic development related to neurological disease.
Tell us about the current biomarker landscape in neurology?
We are seeing a time of extraordinary acceleration and expansion in biomarker and diagnostics developments in Neurology.
This is due a convergence of a number of factors:
First, clinical trials in neurology have become highly reliant on relevant biomarkers as surrogate endpoints for target engagement and treatment response measures in lieu of behavioral or functional measures. Meanwhile, there has been a drive to improve outcomes and reduce trial expenses by identifying peripheral biomarkers that have concordance with central pathology and employing them in patient selection. In Alzheimer’s disease for example, definitive diagnosis of disease often requires amyloid PET scans, which are expensive involve exposure to radiation and require proximity to a cyclotron. Recently, we’ve seen the development of fluid biomarkers, both in CSF and blood that are concordant with amyloid PET. The blood assays, which are somewhat less accurate than CSF assays are increasingly being used to triage subjects entering clinical trials, while the highly accurate CSF assays are being used as a replacement for PET.
Secondly, all of these drug discovery efforts have led to first FDA approved disease modifying therapies for Alzheimer’s and ALS with other potential therapies following close behind. With those therapies come the need to accurately identify the most appropriate patients for access to those drugs. For example, in Alzheimer’s disease, an amyloid targeting drug should only be given to a patient who has amyloid pathology. As I mentioned, CSF assays are concordant with PET scans and cost thousands of dollars less. Labcorp developed a test to identify patients who could benefit from amyloid targeting treatments, and Fujirebio has received the first FDA approval for an Alzheimer’s disease diagnostic test based upon a fluid biomarker. For Parkinson’s disease there is a CSF assay being offered as a diagnostic. So the power of fluid biomarkers are being developed into diagnostics for clinical practice.
Finally, there have been advances in assay platforms that now offer a number of robust reproducible high-throughput ultra-high sensitivity assays. We are often able to offer assays targeting the same biomarker on multiple competing platforms.
Compared with other therapeutic areas, what are the key differences for the development of a biomarker for neurology?
The brain is relatively isolated from the bloodstream or systemic circulation by the blood-brain barrier. Because brain proteins need to cross this barrier, brain biomarkers are found in very low concentrations in blood and require high sensitivity assays for detection.
Neurology biomarker discovery often requires first establishing the importance of a biomarker in cerebrospinal fluid which is obtained by lumbar puncture. Since this is a far more invasive procedure than a blood draw, CSF samples are difficult to obtain.
Neurology biomarkers themselves often have challenging characteristics. They tend to aggregate, stick to tubes, and are often sensitive to mixing. It has taken years of collaborative international research to establish the necessary pre-analytical handling procedures for many of these.
What impact will advancements in neurology biomarkers have in the next several years?
Over the next several years, neurology biomarkers will increasingly find their way into the patient journey as part of clinical practice and will be developed as clinical diagnostics. This progress will be accelerated by the availability of minimally invasive blood biomarkers. What individual biomarkers might lack in sensitivity or specificity will be compensated for with panels of several biomarkers combined into an algorithm.
A recent consensus statement from the Alzheimer’s Association supports the current use of blood based biomarkers for research purposes, but finds that more research is needed before they are adopted for clinical practice. In part this is because there is a stigma associated with dementia, and there are risks associated with a diagnosis of dementia in the absence of available therapies, such as loss of insurance, isolation, life disruption, and self-censoring. However, as disease modifying therapies reach the market over the next few years, the risks associated with a diagnosis will diminish significantly.
We’ll also see the application of biomarker to measure brain health, perhaps as a routine component of health care. There is an epidemic of brain injury in this country resulting from falls, accidents, sports and abuse and much of it goes unreported inviting even more extensive often permanent injury. Labcorp now offers a lab developed test for neurofilament light, a marker for nerve injury regardless of cause, and we’re investigating other makers as well that could be useful to monitor concussion, for example. Imagine someone who suffers a concussion while playing sports having a test that will inform whether it is safe to return to play. That’s in our future within the next few years.