The world has been waiting for an Alzheimer’s disease (AD) blood test – a way to aid in the diagnosis of Alzheimer’s using a simple blood sample that can be obtained in a physician’s office. A test like that can provide individuals and their families with an earlier, easier start to managing AD, and also holds promise for speeding up Alzheimer’s drug development by making clinical trial enrollment more efficient. Equally important, it can help to rule out Alzheimer’s as a cause of an individual’s memory decline, prompting the clinician to search for other conditions that may be treatable or even reversible.
Now the wait is over. Aided by key early funding from BrightFocus, late last year, the PrecivityAD blood test, developed by C2N Diagnostics, entered the commercial market for use by physicians to support their patient care. In research settings, the PrecivityAD test consistently identifies the presence of brain amyloid, a pathologic hallmark of AD. The test has an overall agreement of approximately 86 percent with brain amyloid PET to detect the presence or absence of amyloid plaques. This result occurs from a single blood draw and combines the blood ratio of Aβ42/40 with a person’s age and APOE genotype (another factor analyzed with the test).
Over the past two decades, the BrightFocus Alzheimer’s Disease Research (ADR) program has provided grant support for the research of David Holtzman, MD, and Randall Bateman, MD, both of Washington University School of Medicine, who discovered techniques used in the test, and to Phil Verghese, PhD and Joel Braunstein, MD, MBA at C2N Diagnostics, the small but mighty St. Louis-based biotech company founded by Holtzman, Bateman and colleagues in 2007, which was tasked with commercially developing the first-ever Alzheimer’s blood test for market.
In October 2020, the efforts of the many researchers involved in the project paid off. C2N’s PrecivityAD blood test was introduced under the Clinical Laboratory Improvement Amendments (CLIA) regulations for patient care as a clinical laboratory test in the majority of states. The test is available in all but two states, Maryland and New York (which have separate CLIA certification requirements that are expected to be satisfied soon) and Puerto Rico. The test also has been approved for sale in European Union countries.
In the following Q and A, Joel Braunstein, MD, MBA, president, CEO, and cofounder of C2N, describes how the PrecivityAD test is being used in clinical practice. Importantly, the company is providing one-on-one support to office-based physicians who are using it to care for Alzheimer’s patients.
BrightFocus: How will the PrecivityAD test be of benefit to patients, both now and in the future, when disease-modifying drugs for Alzheimer’s become available?
Dr. Braunstein: Patients and the medical community are already benefiting from the PrecivityAD blood test. It is helping physicians better determine for their patients the presence or absence of amyloid plaques in the brain, a hallmark sign of Alzheimer’s disease. We believe the PrecivityAD test is substantially less invasive, more convenient, and less costly than other methods for identifying brain amyloid. It’s a widely accessible diagnostic tool for health care providers to use with patients experiencing memory complaints.
The earlier a patient receives an Alzheimer’s diagnosis, the earlier a care plan can be put in place for the patient, and other options such as clinical research can be explored. AD clinical trials take many forms, including prevention trials and trials testing novel treatment strategies at the earliest stages of the disease. When disease modifying therapies and other treatments for Alzheimer’s disease become available, the PrecivityAD test will help physicians to identify disease at early stages. Early diagnosis will lead to earlier intervention, which will likely translate to better clinical outcomes for patients.
In addition, many physicians understand that diagnosing Alzheimer’s disease based on clinical criteria alone is both challenging and uncertain. This leads to high misdiagnosis rates among patients with early signs of cognitive impairment, which can be distressing for the patient and their families. Incorrect diagnosis also has the potential to delay an individuals’ access to proper care, particularly for those forms of non-Alzheimer’s dementia that are treatable or even possibly reversible.
BrightFocus: How accurate is the test compared to other diagnostic methods?
Dr. Braunstein: Currently, the conventional approach for detecting Alzheimer’s pathology is through PET imaging or cerebrospinal fluid analysis to visualize and/or measure brain amyloid deposits. Our previous research has shown that the PrecivityAD test can reliably identify or rule out the presence of brain amyloid accumulation with an overall agreement with amyloid PET of around 86 percent. In a study from Washington University School of Medicine, Dr. Schindler and colleagues also found that the measurements we make in the PrecivityAD test were abnormal before – in some cases, years before – the PET scan became abnormal, suggesting that the blood test measurements are highly sensitive for detecting the earliest stages of amyloid buildup in the brain (Neurology, 2019)
In real life, however, what often happens is that clinicians diagnose AD in the office based on self-reporting of symptoms by an individual and his/her care partner. We know that it is possible to do better; however, as a recent study reports, a physician’s clinical diagnosis of AD, as compared to neuropathology (eg PET imaging or CSF analysis), has a sensitivity ranging from 70.9 percent to 87.3 percent and a specificity ranging from 44.3 percent to 70.8 percent. From these published data, it is evident that the clinical diagnosis of AD made by physicians is associated with false positives (29.2 percent to 55.7 percent) and false negatives (12.7 percent to 29.1 percent). This underscores the vital importance of biomarkers that detect disease pathology to improve the accuracy of clinical diagnosis.
BrightFocus: What is the cost of the test?
Dr. Braunstein: The PrecivityAD blood test has a list price of $1,250 and, as a new test, it is not currently covered by private insurance providers, or by Medicare and Medicaid. Patients are responsible for paying for the test out-of-pocket. However, C₂N Diagnostics is committed to making the test available to all patients who need it, and a financial assistance program is available for those patients that medically and financially qualify. A six-month, interest-free payment plan is also available. Patients can call (855) 489-1206 for more information about payment options. In addition, C₂N is working to establish reimbursement for the PrecivityAD test.
BrightFocus: Won’t many people want to have the test right away?
Dr. Braunstein: As one might expect, this is a very personal decision for people. However, as a general rule of thumb in medicine, the more informed an individual is with regard to his/her own health, the more proactive that person can be to identify the best strategies to cope with and manage his/her condition.
With growing age, many people worry at some point about whether they might have the beginning of Alzheimer’s. For now, the PrecivityAD blood test is medically indicated only for people who are experiencing memory and thinking challenges. It is not a screening test for otherwise healthy people. Any qualified health care provider can order the PrecivityAD test, and it is recommended specifically for patients 60 and older who are experiencing cognitive impairment, such as memory decline or other issues related to dementia.
In other words, this test is not currently appropriate for people who are worried about Alzheimer’s, and who may even have a family history of Alzheimer’s, but who themselves have no actual Alzheimer’s symptoms at this time. For those people, it helps to have a good relationship with a doctor, and an open and frank discussion about Alzheimer’s symptoms if they occur.
BrightFocus: Are clinicians ready for a blood test that reliably detects Alzheimer’s disease? Will they be nervous about how to give results like this to their patients? On the other hand, will a test like this make it possible for a broader range of clinicians, including primary care providers in geriatrics, internal medicine, and family practice, to diagnose and treat Alzheimer’s?
Dr. Braunstein: Clinical interest in the PrecivityAD test has come from many sources, including large healthcare systems, academic-based and private Alzheimer’s disease research centers, large and small physician practices, as well as individual neurologists, internists, geriatricians, general practitioners and other physicians. There are no limitations on the types of health care providers that can order the test, but C2N does have an assessment process (see next response) to ensure that health care providers are prepared to properly order the test, use the results to assist in their clinical evaluation of the patient, and manage the communication of results with patients and their families.
Like their patients, health care providers are seeking diagnostics tools that are widely accessible, less invasive and able to help turn a confusing clinical picture into one with more diagnostic clarity.
BrightFocus: How is C2N providing support to clinicians who want to use the PrecivityAD test in practice?
Dr. Braunstein: C2N is very interested in partnering with health care providers to ensure they are well prepared to start using the PrecivityAD test in their clinical practice. We typically arrange a conference call with one or more clinicians and ancillary personnel from the clinical site to review the following aspects of the PrecivityAD test: intended use, test data, Results and Interpretation Report, and the blood draw process. C2N leadership makes it a priority to be available for speaking with health care providers to answer any questions about the test and for discussions of the test report that is shared with patients.
C2N is also committed to ongoing clinical research with investigators to understand how its biomarkers, including the PrecivityAD test, can improve clinical care and speed access to innovative treatments under development. Health care providers and patients can visit www.precivityad.com or call the C2N toll-free number 1.877.226.3424 or to learn more about the test.
BrightFocus: Amyloid plaques are one marker of AD, and there are others. Is C2N moving ahead to develop tests to measure tau and additional factors as part of a screening/diagnostic panel for Alzheimer’s?
Dr. Braunstein: Over time, additional markers, including tau-related analytes and other markers of brain injury, will be added to the PrecivityAD test as part of a C2N Brain Health Panel. Our team of scientists at C2N is making excellent progress on the development of these markers, and we expect over time to introduce them into the clinic in a way that will assist physicians with better disease identification, differential diagnosis, disease staging, prognosis and prediction of future events, and responses to therapy.
BrightFocus: Will you be seeking FDA approval for the PrecivityAD test?
Dr. Braunstein: Yes, the process to obtain FDA approval for the PrecivityAD test has already begun. In 2019, recognizing the major unmet need for blood-based diagnostic tests to identify AD earlier than current practice allows, the FDA granted C2N a “Breakthrough Device” designation for the PrecivityAD test through a federal program designed to accelerate the path to approval. This year, we have already made great progress toward the goal of completing the requisite work needed before filing for FDA approval. Within the last month, C2N has also published two studies demonstrating the excellent clinical and analytical performance of the test in peer-reviewed journals (See West et al, Mol Neurodegen 2021; and Kirmess et al, Clin Chem Acta 2021 [In Press]) with additional manuscripts from other clinical studies in progress.
The process by which we have introduced the PrecivityAD test into the clinic, through CLIA and our CE Mark in Europe, has enabled patients and physicians to already start benefitting from access to this important technology. In recent months, with such an advanced test, we have also been able to provide clinical researchers and pharmaceutical companies with a new tool that is helping to address complex scientific questions relating to AD.
BrightFocus: What can you say to BrightFocus donors whose contributions over the past decades helped support the discovery and development of this first-ever AD blood test?
Dr. Braunstein: BrightFocus has played an important role in this breakthrough and we are very grateful. From the initial stages to where we are today, support from BrightFocus has been a vital part of our success. Our experience exemplifies what BrightFocus means when it says “research equals hope.”
- A Blood Sample Speeds Alzheimer’s Diagnosis (BrightFocus Research in Brief, 2021)
- BrightFocus An Early Supporter of Game-Changing New Alzheimer’s Disease Blood Test (Science News story, 2021)
- Encouraging Sign for Alzheimer’s Blood Test in BrightFocus-Funded Study (BrightFocus News Release, 2019)
- BrightFocus-funded Alzheimer’s Test Gets Encouraging Sign from FDA (Science News story, 2019)
- BrightFocus Grantee Seeks Closer Knowledge of Amyloid-Beta Plaques in Alzheimer’s Disease (Science News story, 2018)
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