ADx NeuroSciences might be described best as the Intel of biomarker assays for neuro-degenerative disease. They don’t create complete kits, but their top-notch biomaterials are included in the assays detecting disorders from Alzheimer’s disease to ALS to traumatic brain injury. Over the years, ADx has created an extensive network of partners and by combining knowledge and expertise, these collaborations are leading to innovative markers and valuable new insights in neurodegenerative diseases.
"The pharmaceutical industry is in need of objective and effcient methods to diagnose neurodegenerative diseases, more specifically in early stages,” explains Koen Dewaele, CEO at ADx NeuroSciences. “In clinical trials, being able to select the right patients and stratify them into groups is of crucial importance. This way, the right conclusions can be drawn from the data that these trials provide. Determining whether or not a therapy is effective can largely be dependent on the patient selection process.”
With more than 25 years of experience in diagnostics, Dewaele knows what he is talking about. Together with three colleagues, he led Innogenetics’ Alzheimer’s division, and when the company dissolved in 2011, the four companions decided to start their own company revolving around Alzheimer’s diagnosis: ADx NeuroSciences.
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Knowing your place
Although diagnostics for neurodegenerative diseases is ADx’s focus, the company is not a classic IVD company; instead, it occupies a unique place in the market. ADx offers services to both IVD and pharmaceutical companies.
“For pharmaceutical companies, we take a custom approach. We look at the goal of a certain clinical trial and deliver custom products and support in collaboration with our IVD partners. We help labs to select the right tests and perform them in a validated manner for clinical trials. Sometimes our pharmaceutical clients have very specific needs. In those cases, we help our IVD partner in adding modifcations to their products. Through this three-way alliance between ADx, pharma and IVD partners, we bring fit-for-purpose solutions to pharmaceutical companies.”
Since partnering is central to ADx’s strategy, their network is impressive. Next to IVD and pharma, collaborations with academic institutes form the third pillar of ADx’s business model.
“Universities and other academic institutions provide access to new antibodies and human samples for testing and validating our assays. Their research leads to innovative biomarkers or new insights into disease states, which is invaluable for a company that wishes to bring these innovations to the clinic. Our academic partners are also important promoters of our company. Co-authorship on important publications emphasizes ADx’s search for novelty, and principle investigators that are approached by pharmaceutical companies for clinical trials can facilitate collaborations that includes ADx. They can decide to implement our tests in trial protocols.”
“The materials we use are a mix of licensed molecules from universities and materials developed in house. We’re not suffering from the so-called not-invented-here syndrome, where all external input is avoided or distrusted. We simply use the best materials. Sometimes we find them with an external partner, and sometimes our own materials outperform the rest. Our neurogranin and phospho-tau antibodies, for instance, were fully developed in-house.”
The FDA delay
Despite the fact that some classic markers for neurodegeneration, such as amyloid-β and tau, have been around for years, the market of neurodegenerative biomarkers is still in its infancy. Dewaele is confident that this will rapidly change once therapies and medicines become available that rely on biomarkers for correct application. However, one essential hurdle still needs to be overcome: "We can see that acceptance of the use of these markers in clinical trials is growing rather slowly, as they're not officially approved by the authorities. FDA approval is crucial to demonstrate the robustness of a test and that it is manufactured according to certain standards. The fact that none of the neurological markers are FDA-approved at present causes pharmaceutical companies to remain skeptical. Many companies like ours are looking into the possible trajectory to get approval because it would be a hugely important milestone for the entire industry. Everyone in the business feels that these markers are full of potential and are making beautiful progress. Once the first marker is approved, others will swiftly follow. FDA approval is really necessary to break through to the routine market."
Getting biomarker tests to be routinely used in clinical trials is a second important factor that would significantly expand the market. Neurodegenerative markers can act as companion diagnostics, guiding researchers and caregivers in the decision-making process. Once therapies that benefit from biomarker information are commercialized, reimbursement of these assays can be considered. Dewaele elaborates: “The aging population and related increase in neurodegenerative disease prevalence will greatly increase the need for biomarker assays. Whether these assays will be reimbursed will entirely depend on the benefits they provide: If these tests give crucial information regarding medicine dosage or patient profiling, insurance companies will most definitely cover the costs. Treatments themselves are always much more expensive than the accompanying assay, and if the assay can cut back on unnecessary treatments, insurances will find the test worthwhile, no matter how expensive the test may be. Currently, there is no reason to reimburse the test, because there is simply no validated treatment available for many neurological diseases. Because of that, we can’t act on the information biomarkers can provide.”
More markers in more diseases
While awaiting the first FDA-approved biomarker, research isn't standing still. As more and more is uncovered about the pathological processes of Alzheimer’s and other neurodegenerative diseases, the role and importance of biological markers become more pronounced, especially in an early stage of the disease.
"While amyloid-β and tau are the most established markers within Alzheimer's disease, we are starting to notice how these are not revealing everything. Amyloid-β accumulation can start very early, up to 20 years before the first symptoms of Alzheimer's disease appear. This gives us the opportunity to detect the disease early on, but also means that amyloid is not very suitable for assessing disease symptoms. The neurodegenerative field is focusing more and more on synaptic markers, as the synapses are good indicators of the overall health of neurons. When the synapses start to degenerate, we know that disease symptoms won't be far away. Although amyloid can indicate Alzheimer's pathology, as long as the synapses remain intact, patients won't become sick.
Each biomarker gives away a specific piece of information, gradually revealing a patient's condition.
“While amyloid can be used as a diagnostic marker, synaptic markers such as neurogranin confer information about the patient’s prognosis. For example, this innovative marker can indicate whether a patient will progress to symptomatic disease within one or five years. Again, this is very valuable information for pharmaceutical companies. If these groups can't be distinguished, it's very hard to determine the effectiveness of a therapy or treatment method.
While we initially focused on Alzheimer's disease, we noticed that many of the markers relevant in Alzheimer’s are also popping up in other neurological disorders. Alzheimer's disease was pioneering in the research for neurodegenerative biomarkers, but the field is now expanding to Parkinson's disease, MS, ALS and brain trauma. A good example is tau, a marker for neuron damage in Alzheimer’s disease. We know that tau is also released into the bloodstream after a concussion, so the protein can also serve as a marker for traumatic brain injury.”
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Century of the brain
Although the market is still in an early stage, there is no doubt that biomarkers will play an important role in patient diagnosis, prognosis, monitoring and treatment for neurological diseases. Knowledge about the field is growing rapidly, and ADx is ready to bring this knowledge to the physicians and patients. Their unique antibodies for detecting neurological markers rank among the world’s best.
The quality of our biomaterials is the best on the market. You can easily find antibodies online, but they can’t be bought in large quantities, are terribly expensive and often not in conditions or of sufficient quality to use in assay design. We produce state-of-the-art antibodies, ideally suited for biomarker detection and implementation on various technology platforms.
The 21st century in medicine will definitely be the century of the brain. Vast uncharted territories are being explored in neurology, new methods and models are becoming available and early diagnostics are giving a new impulse to treatment research. Dewaele concludes: "With ADx, we are gradually building a neurodiagnostic company that contributes significantly to the wellbeing of patients suffering from a broad range of neurodegenerative diseases.”
This article appears in the BioVox White Paper on In Vitro Diagnostics, May 2016. Download the complete work here for free.