NEW YORK ─ Fujirebio Diagnostics expects a decision during the first quarter of this year about a submission to the US Food and Drug Administration for clearance for its Lumipulse G β-Amyloid Ratio (1-42/1-40) diagnostic test.
A green light from the FDA would represent the first such clearance for an Alzheimer's diagnostic assay in the US and, according to Hiroshi Sekiya, Fujiribio's senior manager of product and customer management, broaden adoption of the firm's in vitro diagnostic assays for Alzheimer's that are already gaining traction in Europe.
The company announced in December it had applied to the FDA for clearance for its Lumipulse G β-Amyloid Ratio (1-42/1-40) diagnostic test, which runs on the firm's fully automated Lumipulse G1200 instrument.
The assay measures concentrations of β-Amyloid1-42 and β-Amyloid1-40 peptides in cerebrospinal fluid and provides a numerical ratio that, according to the firm, is better than CSF Aβ1-42 alone in detecting brain amyloid deposition related to Alzheimer's. The ratio can also help in the differentiation of Alzheimer's from non-Alzheimer's dementias, and reduce variability due to preanalytical differences during testing, the firm said.
Specifically, its semiquantitative assay can be used with adults aged 50 years-and-over who present with cognitive impairment that are being evaluated for Alzheimer’s disease and other causes of cognitive decline, according to Fujirebio, which received FDA Breakthrough Device Designation for the test in February 2019.
Fujirebio intends to market the test to hospital and reference labs in the US, Sekiya said.
With CE marking obtained in 2017, the firm is already seeing more than 50,000 of its Alzheimer's disease diagnostic tests being performed each year in memory clinics associated with hospitals in Europe and other regions that accept the regulatory designation.
The Alzheimer's tests run on its Lumipulse platform, which is a sample-in, results-out system with a turnaround time of about 30 minutes. Each Lumipulse platform can complete up to 120 tests per hour, making it suitable for medium- and high-throughput laboratories, Sekiya said.
The availability of such a diagnostic test for Alzheimer's cannot come soon enough for many industry insiders. The prospect of the β-Amyloid ratio test becoming available in the US is welcome news, said Paul Kinnon, CEO of Milan, Italy-based Diadem, which is also developing a blood-based test for Alzheimer's.
Being able to detect and predict the disease before the patient is diagnosed is one of the biggest challenges in the field, he noted, because brain pathology associated with Alzheimer’s begins years before patients are symptomatic.
"To impact disease progression in a meaningful way, early identification is essential, and the current portfolio of clinical tests cannot accomplish this goal," said Kinnon. Tests that enable early detection for Alzheimer's, he added, "will inform treatment by making definitive diagnoses far more feasible."
FDA's decision about Fujirebio's assay is anticipated at a time of increasing regulatory activity associated with amyloid-beta biomarkers, not only for early Alzheimer's disease detection but also for drug development.
The agency is expected to decide in early March on a Biologics License Application for aducanumab, an investigational treatment for Alzheimer’s disease being developed by Cambridge, Massachusetts-based Biogen and Tokyo-based Eisai.
Biogen has used Fujirebio's Lumipulse G β-Amyloid Ratio (1-42/1-40) diagnostic test for its clinical trial data analysis, Sekiya said, adding that the firm is partnering with all major pharma companies developing Alzheimer's therapies.
An FDA go-ahead for Fujirebio's test and Biogen's drug would mean clinicians looking to prescribe the drug can use the test to identify suitable patients, he added.
In the US, where the firm has headquarters in Malvern, Pennsylvania, its collaboration with Biogen covers not just clinical trials but also the planning of future commercial activities for its assay, Sekiya said.
For growth and future sales within its neurodegenerative disease test portfolio, Fujirebio is not relying solely on the FDA decision about the drug or its own diagnostic test. Following CE marking, European memory clinics affiliated with hospitals began conducting diagnostic tests using the Lumipulse G Alzheimer's disease assays a few years ago, Sekiya said. The company obtained the designation in 2017 for Lumipulse G β-Amyloid 1-42 and Lumipulse G Total Tau chemiluminescent enzyme immunoassay kits running on its Lumipulse systems.
Tests using the different types of Alzheimer's biomarker assays can be run simultaneously on Lumipulse systems to increase the sensitivity of overall testing and provide additional inputs for clinicians, Sekiya said. The systems enable random-access testing, or the ability to be plugged in and run tests using one assay while other assays and tests are already being run.
The company plans to seek FDA clearance for another Alzheimer's test based on a signature for the tau protein, but a timeline for its submission is not yet available, Sekiya said.
Further, it intends to seek clearance in Asia and Latin America for its Lumipulse G β-Amyloid Ratio (1-42/1-40) diagnostic test for Alzheimer's. In Japan, the company is working in parallel with pharmaceutical companies, he said, to submit combined applications for drug approvals and its assay, and it expects to receive marketing approval there sometime this year.
US-based Fujirebio Diagnostics, a wholly-owned subsidiary of Fujirebio Holdings and HU Group Holdings, both based in Tokyo, believes that its assays can detect amyloid proteins that are indicative of a future buildup of amyloid plaque up to two years before they can be seen by PET imaging.
But measuring amyloid-beta buildup often requires collecting CSF via a spinal tap, which could be a challenge to adoption, and Kinnon said that the use of CSF samples for Fujirebio's test "will likely limit its use to some extent."
The barrier to collecting blood is far lower than for CSF, and if blood-based assays can be made available they could eventually be used to screen patients for Alzheimer's during annual exams.
As a result, Fujirebio is developing blood-based tests, including those that leverage amyloid-beta and neurofilament light. A blood-based phosphorylated tau assay that it is currently developing may be the closest to commercialization, Sekiya said, but is too early in its development to disclose a potential timeline for launch.
Other companies, seeing an opportunity to improve on CSF-based tests, are also developing blood-based assays.
St. Louis-based C2N Diagnostics in November became the first company to bring a blood-based test for Alzheimer's to market and recently announced approval from the state of California to test patients out of a CLIA facility.
Kinnon's Diadem is developing a blood-based test, AlzoSure Predict, that uses an antibody to target changes in the p53 protein. He said the test will be able to predict when individuals will experience an "early onset of decline into Alzheimer’s at least six years in advance of current methods of diagnosing the disease."
Sekiya said that Fujirebio may have advantages over new competitors because it has been in the neurodegenerative disease diagnostics space for more than 20 years. If the FDA clears its test, the firm's "big next step will be to seek reimbursement," he said.
To that end, the company sees many peer-reviewed, published clinical studies involving the use of its Alzheimer's assays, he noted. One such study published in November 2019 in BMC Alzheimer's Research & Therapy compared its β-Amyloid1-42 and β-Amyloid1-40 ratio test with other Alzheimer's biomarkers and found that the ratio-based test had a sensitivity of 97.5 percent and specificity of 92.5 percent.