As new diagnostic assays are cleared by regulators, clinical laboratories will play a key role in identifying appropriate patients for new less-invasive Alzheimer’s tests
With multiple companies racing to develop a blood-based test for Alzheimer’s disease (AD), clinical laboratories may soon have new less-invasive diagnostic assays for AD on their menus.
Why a race? Because a less-invasive clinical laboratory test that uses a venous blood draw (as opposed to a spinal tap)—and which has increased sensitivity/specificity—has a potentially large market given the substantial numbers of elderly predicted to develop Alzheimer’s over the next decade. It has the potential to be a high volume, high dollar diagnostic test.
In fact, Mordor Intelligence estimates that the market for Alzheimer’s disease therapeutics will grow from $7.7 billion in 2024 to $10.10 billion by 2029.
Alzheimers.gov, an official website of the US government, says, “Researchers have made significant progress in developing, testing, and validating biomarkers that detect signs of the disease process. For example, in addition to PET scans that detect abnormal beta-amyloid plaques and tau tangles [abnormal forms of tau protein] in the brain, NIH-supported scientists have developed the first commercial blood test for Alzheimer’s. This test and others in development can not only help support diagnosis but also be used to screen volunteers for research studies.”
Additionally, the US Food and Drug Administration (FDA) is clearing new Alzheimer’s drugs for clinical use. The pharma companies behind these drugs need clinical laboratory tests that accurately diagnosis the disease and confirm that it would be appropriate for the patient to receive the new therapeutic drugs, a key element of precision medicine.
“The big promise for blood tests is that they will eventually be accessible, hopefully, cost-effective, and noninvasive,” Rebecca Edelmayer, PhD (above), Vice President, Scientific Engagement, Alzheimer’s Association, told USA Today. “The field is really moving forward with use of these types of tests,” she added. Clinical laboratories may soon have these new assays on their test menus. (Photo copyright: Alzheimer’s Association.)
Companies in the Race to Develop Blood-based Alzheimer’s Tests
Researchers found that C2N’s blood test can detect brain amyloid status with “sensitivity, specificity, positive and negative predictive values that approximate those of amyloid positron emission tomography (PET) imaging,” according to a news release.
“The PrecivityAD2 blood test is intended for use in patients aged 55 and older with signs or symptoms of mild cognitive impairment or dementia who are undergoing evaluation of Alzheimer’s disease or dementia. Only a healthcare provider can order the PrecivityAD2 test,” the news release noted.
“The PrecivityAD2 blood test showed strong clinical validity with excellent agreement with brain amyloidosis by PET,” the researchers wrote.
The PrecivityAD2 test, which is mailed directly by C2N to doctors and researchers, is performed at the company’s CLIA-certified lab, according to USA Today, which added that the cost of $1,450 is generally not covered by insurance plans.
Expanding Test Access with IVD Companies
ALZpath, Inc. has a different approach to the Alzheimer’s disease test market. The Carlsbad, Calif.-based company, set up an agreement with in vitro diagnostics (IVD) company Roche Diagnostics for use of its phosphorylated tau (pTau)217 antibody “to develop and commercialize an Alzheimer’s disease diagnostic blood test that will be offered on the Roche Elecsys platform,” according to a news release.
Roche received FDA breakthrough device designation on the Elecsys pTau217 test earlier this year and will work with pharmaceutical company Eli Lilly to commercialize the test.
Estimates show 75% of dementia cases go undetected—a number which could grow to 140 million by 2050, according to data shared by Roche with Fierce Biotech.
“We plan to leverage our installed base of diagnostic systems, which is the largest in the world, to ensure we are able to create access to this test for those who need it the most,” Matt Sause, CEO, Roche Diagnostics, told Fierce Biotech.
Another IVD company, Beckman Coulter, recently signed an agreement to use ALZpath’s pTau217 antibody test in its DxI 9000 Immunoassay Analyzer. In a news release, Kathleen Orland, SVP and General Manager of the Clinical Chemistry Immunoassay Business Unit at Beckman Coulter, said that the test had “high performance in detecting amyloid pathology” and could “integrate into our advanced DxI 9000 platform to support broad-based testing.”
Clinical Laboratory Participation
The FDA is drafting new guidance titled, “Early Alzheimer’s Disease: Developing Drugs for Treatment” that is “intended to assist sponsors in the clinical development of drugs for the treatment of the stages of sporadic Alzheimer’s disease (AD) that occur before the onset of overt dementia.”
Pharma companies intent on launching new drugs for Alzheimer’s will need medical laboratory tests that accurately diagnosis the disease to confirm the medications would be appropriate for specific patients.
Given development of the aforementioned pTau217 antibody tests, and others featuring different diagnostic technologies, it’s likely clinical laboratories will soon be performing new assays for diagnosing Alzheimer’s disease.
Infection control teams and clinical laboratory managers may want to look at this new product designed to improve the diagnosis and treatment of sepsis
Accurate and fast diagnosis of sepsis for patients arriving in emergency departments is the goal of a new product that was just cleared by the federal Food and Drug Administration (FDA). It is also the newest example of how artificial intelligence (AI) continues to find its way into pathology and clinical laboratory medicine.
Sepsis is one of the deadliest killers in US hospitals. That is why there is interest in the recent action by the FDA to grant marketing authorization for an AI-powered sepsis detection software through the agency’s De Novo Classification Request. The DNCR “provides a marketing pathway to classify novel medical devices for which general controls alone, or general and special controls, provide reasonable assurance of safety and effectiveness for the intended use, but for which there is no legally marketed predicate device,” the FDA’s website states.
Unlike a single analyte assay that is run in a clinical laboratory, Prenosis’ AI/ML software uses 22 diagnostic and predictive parameters, along with ML algorithms, to analyze data and produce a clinically actionable answer on sepsis.
It is important for clinical laboratory managers and pathologists to recognize that this diagnostic approach to sepsis brings together a number of data points commonly found in a patient’s electronic health record (EHR), some of which the lab generated and others the lab did not generate.
“Sepsis is a serious and sometimes deadly complication. Technologies developed to help prevent this condition have the potential to provide a significant benefit to patients,” said Jeff Shuren, MD, JD, Director of the FDA’s Center for Devices and Radiological Health, in a statement. “The FDA’s authorization of the Prenosis Sepsis ImmunoScore software establishes specific premarket and post-market requirements for this device type.” Clinical laboratory EHRs contain some of the data points Prenosis’ diagnostic software uses. (Photo copyright: US Food and Drug Administration.)
How it Works
To assist doctors diagnose sepsis, the ImmunoScore software is first integrated into the patient’s hospital EHR. From there, it leverages 22 parameters including:
White blood cell count to produce a score that informs caregivers of the patient’s risk for sepsis within 24 hours, MedTech Dive reported.
Instead of requiring a doctor or nurse to look at each parameter separately, the SaMD tool uses AI “to evaluate all those markers at once”, CNBC noted. It then produces a risk score and four discrete risk stratification categories (low, medium, high, and very high) which correlate to “a patient’s risk of deterioration” represented by:
By sharing these details—a number from one to 100 for each of the 22 diagnostic and predictive parameters—Sepsis ImmunoScore helps doctors determine which will likely contribute most to the patient’s risk for developing sepsis, MedTech Dive reported.
“A lot of clinicians don’t trust AI products for multiple reasons. We are trying very hard to counter that skepticism by making a tool that was validated by the FDA first, and then the second piece is we’re not trying to replace the clinician,” Bobby Reddy Jr., PhD, Prenosis co-founder and CEO, told MedTech Dive.
Big Biobank and Blood Sample Data
Prenosis, which says its goal is the “enabling [of] precision medicine in acute care” developed Sepsis ImmunoScore using the company’s own biobank and a dataset of more than 100,000 blood samples from more than 25,000 patients.
AI algorithms drew on this biological/clinical dataset—the largest in the world for acute care patients suspected of having serious infections, according to Prenosis—to “elucidate patterns in rapid immune response.”
“It does not work without data, and the data started at Carle,” said critical care specialist Karen White, MD, PhD, Carle Foundation Hospital, St. Louis, MO, in the news release. “The project involved a large number of physicians, research staff, and internal medicine residents at Carle who helped recruit patients, collect data, and samples,” she said.
Opportunity for Clinical Laboratories
Sepsis is a life-threatening condition based on an “extreme response to an infection” that affects nearly 1.7 million adults in the US each year and is responsible for 350,000 deaths, according to US Centers for Disease Control and Prevention (CDC) data.
A non-invasive diagnostic tool like Sepsis ImmunoScore will be a boon to emergency physicians and the patients they treat. Now that the FDA has authorized the SaMD diagnostic tool to go to market, it may not be long before physicians can use the information it produces to save lives.
Clinical laboratory managers inspired by the development of Sepsis ImmunoScore may want to look for similar ways they can take certain lab test results and combine them with other data in an EHR to create intelligence that physicians can use to better treat their patients. The way forward in laboratory medicine will be combining lab test results with other relevant sets of data to create clinically actionable intelligence for physicians, patients, and payers.
Fujifilm acquired Inspirata’s Dynamyx digital pathology technology and business while GE Healthcare announced a partnership with Tribun Health in Europe
Clinical pathology laboratories, especially in the US, have been slow to adopt digital imaging systems. But recent industry deals suggest that the market may soon heat up, at least in the eyes of vendors. These collaborators may hope that, by integrating diagnostic data, the accuracy and productivity of anatomic pathologists will improve while also shortening the time to diagnosis.
In the press release, Fujifilm stated that 85% of US healthcare organizations use analog systems for pathology. That compares with 86% in Europe and 90% in Asia, the company stated.
“Acquiring Inspirata’s digital pathology business allows Fujifilm to be an even stronger healthcare partner—bridging a technological gap between pathology, radiology, and oncology to facilitate a more collaborative approach to care delivery across the enterprise,” said Fujifilm CEO and president Teiichi Goto in the press release.
The press release cited data from Signify Research, a healthcare technology marketing data firm that is predicting the global market for digital pathology systems would double from $320 million in 2021 to $640 million by 2025.
Fujifilm previously had a deal with Inspirata to sell the Dynamyx system exclusively in the UK, Italy, Spain, Portugal, Belgium, the Netherlands, and Luxembourg, an August press release noted.
“A $320 million global industry in 2021 projected to reach $640 million by 2025, the rising number of cancer cases and the demonstrated benefits of digital pathology are fueling significant demand and market growth in the hospital and pharmaceutical industries,” said Henry Izawa (above), president and CEO, Fujifilm Healthcare Americas Corporation, in a press release. “These evolving clinical needs fuel Fujifilm’s investment and innovation in the digital revolution, and we look forward to introducing Dynamyx and its host of unique features and benefits to our Synapse customers and prospects as we strive to enable more efficient medical diagnosis and high-quality care.” (Photo copyright: LinkedIn.)
In announcing their new collaboration, GE Healthcare and Tribun Health said the integration of their systems—Edison Datalogue and the Tribun Health suite—would foster collaboration between pathologists and clinicians by providing a consolidated location for imaging records. This capability is especially important in oncology, they said.
“The oncology care pathway is one of the most complex with multiple steps involving a variety of specialists, complex tools, frequent decisions, and large data sets,” said GE Healthcare CEO of Enterprise Digital Solutions Nalinikanth Gollagunta in a GE press release. “With this digital pathology collaboration, we continue our journey towards simplifying the oncology care pathway with improved data management, the digitization of pathology, and streamlined data access.”
Tribun Health, based in Paris, France, offers a digital pathology platform that incorporates a camera system, artificial intelligence (AI)-based analysis, remote collaboration, and storage management, plus integration with third-party automation apps.
GE Healthcare claims that Edison Datalogue has the largest share of the Vendor Neutral Archive (VNA) market. That term refers to image archiving systems that use standard formats and interfaces instead of proprietary formats. They are an alternative to the more widely used Picture Archiving and Communications Systems (PACS) used in medical imaging.
The collaboration between the companies “is probably a strategic move to position GE as an integrator of imaging data and digital pathology data in oncology,” said Robert Michel Editor-in-Chief of Dark Daily and its sister publication The Dark Report.
GE’s History with Dynamyx
This is not GE Healthcare’s first foray into digital pathology. In fact, the company had a major hand in launching the very Dynamyx system that Fujifilm recently acquired.
In “GE Healthcare Sells Omnyx to Inspirata,” The Dark Report interviewed Inspirata CEO Satish Sanan who at that time said the acquisition would allow his company to offer “a fully integrated, end-to-end digital pathology solution” in Canada and Europe. But GE Healthcare chose to end the partnership in 2016, citing regulatory uncertainty and variable global demand. Two years later, GE sold Omnyx to Inspirata.
GE Healthcare’s new collaboration with Tribun Health shows that the company “still recognizes the value of the pathology data in cancer diagnosis and wants to be in a position to manage that digital pathology data,” Michel said.
Fujifilm’s Plans
Fujifilm said it will incorporate Dynamyx into its Synapse Enterprise Imaging suite, which includes VNA, Radiology PACS, and Cardiology PACS. “Future releases of Dynamyx will also create opportunities for Fujifilm to support pharmaceutical and contract research organizations with toxicity testing data management for drug development,” the company stated in the press release.
With its recent moves into digital pathology, Fujifilm will be taking on major competitors including Philips, Danaher, and Roche, MedTech Dive reported.
Decision is part of UK effort to diagnose 75% of all cancers at stage I or stage II by 2028 and demonstrates to pathologists that the technology used in liquid biopsy tests is improving at a fast pace
Pathologists and medical laboratory scientists know that when it comes to liquid biopsy tests to detect cancer, there is plenty of both hope and hype. Nevertheless, following a successful pilot study at the Christie NHS Foundation Trust in Manchester, England, which ran from 2015-2021, the UK’s National Health Service (NHS) is pushing forward with the use of liquid biopsy tests for certain cancer patients, The Guardian reported.
NHS’ decision to roll out the widespread use of liquid biopsies—a screening tool used to search for cancer cells or pieces of DNA from tumor cells in a blood sample—across the UK is a hopeful sign that ongoing improvements in this diagnostic technology are reaching a point where it may be consistently reliable when used in clinical settings.
The national program provides personalized drug therapies based on the genetic markers found in the blood tests of cancer patients who have solid tumors and are otherwise out of treatment options. The liquid biopsy creates, in essence, a match-making service for patients and clinical trials.
Liquid Biopsy Genetic Testing for Cancer Patients
“The learnings from our original ‘Target’ study in Manchester were that genetic testing needs to be done on a large scale to identify rare genetic mutations and that broader access to medicines through clinical trials being undertaken across the country rather than just one site are required,” Matthew Krebs, PhD, Clinical Senior Lecturer in Experimental Cancer Medicine at the University of Manchester, told The Guardian.
Krebs, an honorary consultant in medical oncology at the Christie NHS Foundation Trust, led the Target National pilot study.
“This study will allow thousands of cancer patients in the UK to access genetic testing via a liquid biopsy. This will enable us to identify rare genetic mutations that in some patients could mean access to life-changing experimental medicines that can provide great treatment responses, where there are otherwise limited or no other treatment options available.”
Detecting cancers at earlier stages of disease—when treatment is more likely to result in improved survival—has become a strategic cancer planning priority in the UK, theBMJ noted.
“The NHS is committed to diagnosing 75% of all cancers at stage I or II by 2028, from around 50% currently,” the BMJ wrote. “Achieving such progress in less than a decade would be highly ambitious, even without disruption caused by the COVID-19 pandemic. In this context, considerable hope has been expressed that blood tests for circulating free DNA—sometimes known as liquid biopsy—could help achieve earlier detection of cancers.”
The Guardian noted that the UK’s initiative will use a liquid biopsy test made by Swiss-healthcare giant Roche.
“We can’t guarantee that we will find a fault in the genetic code of every cancer patient we recruit, or that if we do, there will be a suitable drug trial for them,” Matthew Krebs, PhD (above), lead scientist of the NHS’ Target National pilot study, told The Guardian. “However, as we learn more about the genetics of cancer in this study, it will help doctors and scientists develop new treatments to help people in the future. Ultimately, we hope liquid biopsy testing will be adopted into routine NHS care, but we need studies such as this to show the benefit of the test on a large scale and provide the evidence that patients can benefit from being matched to targeted medicines on the basis of the blood test.” (Photo copyright: Cancer Research UK Manchester Centre.)
In her article “The Promise of Liquid Biopsies for Cancer Diagnosis,” published in the American Journal of Managed Care (AJMC) Evidence-based Oncology, serial healthcare entrepreneur and faculty lecturer at Harvard Medical School Liz Kwo, MD, detailed the optimism surrounding the “revolutionary screening tool,” including its potential for:
identifying mechanisms of resistance to therapies,
measuring remaining disease after treatment,
assessing cancer relapse or resistance to treatment, and
eliminating risk surrounding traditional biopsies.
The AJMC article estimated the liquid biopsy market will be valued at $6 billion by 2030. However, Kwo also noted that clinical adoption of liquid biopsies in the US continues to face challenges.
Welch compared the investor hype surrounding liquid biopsies to that of the now-defunct blood testing company Theranos, which lured high-profile investors to pour millions into its unproven diagnostic technology.
“Effective cancer screening requires more than early detection. It also requires that starting therapy earlier helps people live to older ages than they would if they started treatment later,” he wrote. “If that doesn’t happen, liquid biopsies will only lead to people living longer with the knowledge they have a potentially incurable disease without extending their lives. These people would be subjected to cancer therapies and their toxicities earlier, but at a time when they would otherwise be experiencing no cancer-related signs or symptoms.”
And so, while there’s much excitement about the possibility of a minimally invasive way to detect cancer, anatomic pathology groups and clinical laboratories will have to wait and see if the hype and hope surrounding liquid biopsies is substantiated by further research.
New biomarkers for cancer therapies derived from the research could usher in superior clinical laboratory diagnostics that identify a patient’s suitability for personalized drug therapies and treatments
Once approved for clinical use, not only would these biomarkers become targets for specific cancer therapies, they also would require development of new diagnostic tests that anatomic pathologists could use to determine whether a biomarker was present in a patient.
If yes, the drug can be administered. If no, the patient is not a candidate for that drug. Thus, this research may produce both diagnostic biomarkers and therapeutic targets.
Relevance of In-Depth Tumor Profiling to Support Clinical Decision-Making
In the Swiss “Tumor Profiler” (TuPro) project, the research team is examining the cellular composition and biology of tumors of 240 patients with melanoma, ovarian cancer, and acute myeloid leukemia. Recruitment for the study began in 2018. Today, the melanoma cohort is fully enrolled, and the ovarian cancer and acute myeloid leukemia cohorts are nearing complete enrollment.
“The Tumor Profiler Study is an observational clinical study combining a prospective diagnostic approach to assess the relevance of in-depth tumor profiling to support clinical decision-making (“fast diagnostic loop”) with an exploratory approach to improve the biological understanding of disease (“exploratory science loop”),” the TuPro website states.
The graphic above taken from the Tumor Profiler project paper illustrates how the TuPro study’s workflow entails patient enrollment, sample collection, analysis by different technology platforms, and data integration, creation and discussion of molecular research and summary reports, discussion of treatment options in pre-tumor boards and the final treatment decision in tumor boards. (Photo copyright: Cancer Cell.)
In their published paper, the Swiss researchers say these three cancers were selected for the study “based on the potential clinical benefit and availability of sufficient tumor material for simultaneous analysis across all technologies.”
According to a University Hospital Basel blog post, the TuPro project examination of each cancer tumor goes “much further than the limited use of molecular biological methods” used by leading hospitals. “This results in huge amounts of data per patient, which we process and analyze using data science methods,” stated data scientist Gunnar Rätsch, PhD (above), Professor for BiomedicalInformatics at ETH Zurich and one of the study’s corresponding authors, in the blog post. This research could lead to new precision medicine biomarkers for clinical laboratory cancer diagnostics and therapies. (Photo copyright: ETH Zurich.)
The TuPro Project’s findings are available to doctors who analyze them at interdisciplinary tumor board meetings and generate treatment options, creating a “fast diagnostic loop” with an estimated four-week turnaround time from surgery to tumor board. “This approach has the potential to alter current diagnostics and paves the way for the translation of comprehensive molecular profiling into clinical decision-making,” the study’s authors wrote in Cancer Cell.
Could Oncologists Be Making Better Precision Medicine Decisions?
In its writeup on the TuPro Project’s research, Precision Oncology News concluded that the Swiss study “is rooted in the researchers’ notion that oncologists are not making the best personalized treatment decisions for patients by relying just on targeted DNA profiling using next-generation sequencing and digital pathology-based tests.
“The researchers within the TuPro consortium hypothesized that integrating a more comprehensive suite of omics tests could lead to a more complete understanding of patients’ tumors, including providing insights into the tumor microenvironment, heterogeneity, and ex vivo responses to certain drugs. This, in turn, could help inform the best course of treatment,” Precision Oncology News added.
“With the Tumor Profiler study, we want to show that the widespread use of molecular biological methods in cancer medicine is not only feasible, but also has specific clinical benefits,” said TuPro consortium member Viola Heinzelmann-Schwarz, MD, Head of Gynecological Oncology at University Hospital Basel, in an ET Zurich news release.
New Precision Medicine Biomarkers from TuPro’s Molecular Analysis
Researchers in the study also are investigating whether and what influence the molecular analysis had on doctors’ therapy decisions.
The University Hospital Basal blog notes the long-term benefits of the Tumor Profiler approach is to expand the personalized-medicine therapy options for patients, including determining whether patients would benefit in certain cases “if they were not treated with drugs from standard therapy, but with drugs that have been approved for other types of cancer.”
Anatomic pathologists and clinical laboratory scientists will want to take note of the TuPro project’s ultimate success or failure, since it could usher in changes in cancer treatments and bring about the need for new diagnostic tests for cancer biomarkers.
