Expert Q&A: Full Approval for Alzheimer’s Blood Tests Not Far Off

Recently, Alzheimer’s disease (AD) blood tests based on the biomarker phosphorylated tau at threonine 217 (p-tau217) have been gaining increasing support. Though none have yet received full FDA clearance or approval in the US, some have achieved Breakthrough Device Designation for priority review by the agency. These tests have the potential to make AD diagnosis faster—as well as less invasive and costly—than other options. One such test, the ALZpath Dx assay, was shown to have similar performance to cerebrospinal fluid (CSF) and positron emission tomography (PET) imaging tests in a recent JAMA Neurology study. Andreas Jeromin, PhD, chief scientific officer (CSO) at ALZpath, discusses the current landscape of blood-based AD tests and their future. These blood-based biomarker tests are currently exclusively available as laboratory-developed tests (LDTs), grandfathered before May 6, 2024.

Q: What are some recent developments in Alzheimer’s blood tests?

A: I think the field is settling on p-tau217 being one of the key transformative biomarkers. The opportunity here is to avoid lumbar punctures [with CSF-based tests] and PET imaging, which is not as accessible and scalable. We’ve really opened up opportunities by being able to measure biomarkers in blood, such as p-tau217, that are very closely related to Alzheimer’s pathology in the brain. A number of studies have now shown that p-tau217 is 94 to 95 percent accurate in determining amyloid or tau PET status in the brain. Its performance is very similar to the performance of CSF, which some people consider the gold standard.

One clinical utility of p-tau217 blood tests is to aid the diagnosis of AD-related pathology. P-tau217 is very closely associated and correlates with amyloid and tau pathology in the brain. The other potential utility, which the field is very excited about, is to use this biomarker to measure and monitor treatment response, as there’s at least one approved treatment available and more in development.

Q: Which developments do you find most exciting and why?

A: Beyond p-tau217 as an AD diagnostic, its potential for treatment monitoring could make such treatments accessible and scalable, and could help address some of the bottlenecks in clinical care. If we look at this from a clinical care perspective, depending where you are—Canada, the US, or European countries—there is about a nine-month delay until you can see a specialist. The vision here is that we can move primary care [forward], by using this biomarker in a triaging or screening context as well, to help determine which care patients should be following.

Beyond p-tau217 as a biomarker of amyloid and tau pathology in the brain, there are no parallel developments to create what I call a precision neurology toolbox. So, not just determining if there’s a high likelihood of amyloid or tau pathology in the brain, but is there a probability of other neurological diseases? There are no biomarkers available for clinical use in this space as well. But with today’s developments, at some point in the not-too-distant future, primary care physicians will have a toolbox of biomarkers available to help determine care pathway classification of different neurodegenerative diseases.

Q: What challenges remain to be overcome with these tests?

A: The change of oversight of LDTs by the FDA [could be a challenge]. The majority of blood-based biomarkers in AD or AD-related pathology are currently developed as LDTs.

Also, one of the looming gaps that often comes up in discussions is that there’s currently a lack of test-specific reimbursement. There are generic immunoassay CPT [Current Procedural Terminology] codes available, but they don’t necessarily cover the cost of running the assay. Actually making codes available and having the level of reimbursement tied to specific tests is an ongoing effort. Another focus is to continue promoting clinical implementation, i.e., education of primary care physicians, general specialized neurologists, and all the stakeholders to understand the risks and benefits of using this test—when to use it and when not to use it.

Q: What is the status of these tests in terms of full regulatory approval in the US?

A: There’s a next wave of developments to make blood-based AD biomarker tests available truly as in vitro diagnostics (IVDs). Everything starts in research, and some of the Research Use Only platforms are analytically and clinically validated as LDTs. My personal prediction is that we may see [blood-based Alzheimer’s] IVDs either cleared or approved, depending on predicate devices, as early as 2025 or 2026.

Q: What are the key advantages of such tests for labs over other options?

A: Assuming it’s reimbursed, and I think the Centers for Medicare & Medicaid Services (CMS) will make a positive decision maybe later in the year and private insurers will follow, the cost-effectiveness is a major advantage. Amyloid PET currently is reimbursed by CMS at least once annually, but it’s not scalable, and it is still expensive. With CSF-based tests, there’s concern about the safety of the lumbar puncture as well. The cost effectiveness in addition to the scalability and accessibility of blood-based biomarkers is a major advantage. ALZPath, for example, is actively working on making this available for at-home blood collection. So, potentially, there’s another wave of accessibility and scalability to come. Currently, a patient would have to come to a memory clinic or a patient service center in Canada or the US to have blood drawn. We’re also looking at nontraditional ways of blood collection, something which may become available as early as 2024.

Q: Once these tests enter regular clinical use, what are the most important considerations for labs thinking of adding blood-based AD testing to their test menus?

A: The platform that will be used to establish [these tests], initially as laboratory-developed tests, is one important consideration. These assays, including the ALZPath p-tau217 assay, are now available on multiple ultrasensitive platforms. Other companies have launched p-tau217 tests as well. [Lab leaders will need to consider] if this is just one test to be offered, or is it part of a larger neurology offering? What are some of the volume considerations? Some of the other non-research platforms are what are called random access platforms, where you don’t have to wait until a certain number of samples have been accumulated to analyze those samples. Labs will also need to consider the cost of the analyzer and kit to be utilized.

Q: What does the future of these tests look like?

A: To me, there are two different pieces. It’s at-home blood collection, [and availability] in an IVD platform as a single or multiple biomarkers. We also need to actively continue to advocate on the implementation side, educate the physicians, the clinicians, the neurologists, all the stakeholders involved, patients included, so that a really informed decision can be made. There are various organizations and initiatives working on educational material. Incorporation of guidelines would be a potential next step—really preparing the current and next generation of physicians and neurologists and ensuring that they understand the utility of these tests.

We as a field need to strike a balance, ensuring that this [testing] is made available in an educated, supervised environment, so physicians and patients clearly understand the risks and benefits, and some of the limitations of the test results. What we know and don’t know about the performance will be important to consider. Understanding the limitations is as important as understanding the risks and benefits.

Want more insights on blood-based Alzheimer’s tests? See our Q&A with Alison Green, PhD, head of laboratory sciences at Scottish Brain Sciences.