NEW YORK – With the launch last week of its PrecivityAD test, C2N Diagnostics has become the first company to bring a blood-based test for Alzheimer's to market.
The company anticipates that the test, which uses mass spectrometry to measures levels of amyloid beta (Aβ) and apolipoprotein E in patient blood, will see uptake among physicians looking for additional information to evaluate patients they suspect of having Alzheimer's, and drug companies in need of a quick and relatively inexpensive test for selecting subjects for clinical trials.
St. Louis-based C2N has been among the leaders in development of blood-based tests for Alzheimer's, which has emerged in recent years as a major area of emphasis within the field. Effective non-blood tests for Alzheimer's exist, foremost among them those that measure Aβ in cerebrospinal fluid and PET imaging that detects brain amyloid plaques. While the presence of brain amyloid plaques is. not on its own. confirmation of Alzheimer's, it is characteristic of the disease and can be used in combination with clinical symptoms to make a diagnosis.
Collecting CSF for Aβ measurements requires a spinal tap, however, while PET imaging is expensive, exposes patients to radiation, and is not readily available in all settings. This has presented a challenge for pharma in particular, as drug companies developing anti-Alzheimer's drugs would like to quickly, easily, and inexpensively screen large numbers of people to select subjects with early-stage Alzheimer's who might be most likely to respond to anti-amyloid therapies.
"On the clinical trial side we are working with a variety of collaborators, both academic and in industry, who are now looking to incorporate this marker into their screening protocols because we and others have data that suggest that one could significantly reduce the cost of enrollment and also shorten the time it takes to enroll subjects," said Joel Braunstein, cofounder, president, and CEO of C2N.
He noted that commonly, PET imaging is done as the final step of the enrollment process to confirm that patients do have the brain amyloid pathology characteristic of Alzheimer's. However, a number of patients that make it to this step will not have amyloid pathology, meaning that they will be excluded from the trial, and the time and resources spent qualifying them up to that point are essentially wasted.
"If you can use a blood-based test like this at the earliest stage of the process, then you can potentially significantly reduce the number of people who ultimately get excluded by the PET scan," Braunstein said.
Braunstein added that some pharma firms are also considering using the test in lieu of a PET scan, though he noted that this would likely happen only once more data on the test's effectiveness had been collected.
The PrecivityAD test combines blood Aβ 40, Aβ 42, and apolipoprotein E levels along with patient age to generate a score of 0 to 100, with a higher score indicating a higher likelihood of amyloid plaques.
C2N validated the test in a study of 686 patients with cognitive impairment and a clinical suspicion of Alzheimer's. All 686 underwent amyloid PET imaging, with 378 of them positive for brain amyloid plaques by PET imaging. The test was able to correctly identify brain amyloid status in 86 percent of the 686 patients.
Howard Fillit, founding executive director and chief science officer of the Alzheimer's Drug Discovery Foundation, which has provided $2.8 million over the last decade to C2N to support development of the PrecivityAD test, said he believed it could see substantial uptake in clinical practice.
He said that the convenience of the test could make it a useful tool for evaluating patients presenting with memory problems or other symptoms of Alzheimer's.
"Right now there is a large population of people who are going into their doctor's office with memory complaints, and they are not getting good care," he said. "I'm not sure they are getting proper diagnostic evaluations. The way we practice medicine, visits are relatively brief and they often result in blood tests."
The PrecivityAD test could help doctors do a better job in their limited time by identifying patients likely to have Alzheimer's, Fillit said.
Fillit said that reimbursement would be the key to determining how frequently doctors used the test and noted that although PET imaging for Alzheimer's diagnosis received US Food and Drug Administration approval in 2012, uptake of the technique has been limited in large part due to reimbursement challenges.
Braunstein, likewise, noted that reimbursement has been an issue for PET, and that this potentially provided an opening for PrecivityAD.
"The feedback we have received from physicians is that the test is very expensive for patients to undergo and right now there is not a uniform policy on reimbursement for that test," he said. "Physicians look at is as a useful tool, but it's expensive, and so, they are trying to think of more efficient and more easily accessible tests that an individual can get."
He suggested that a negative result would also be valuable as it would indicate that a patient's cognitive issues are likely not due to Alzheimer's and that other potential causes should be explored.
Braunstein said that C2N is working with insurance companies and government payors to secure coverage for the test but that it is currently available only on a self-pay basis. The list price is $1,250, though the company offers financial assistance that can bring the price down to between $25 and $400.
It offers the test out of its CLIA facility and is able to provide turnaround time of 10 days from receipt of the sample. In May, C2N received a $20 million investment from philanthropic organization GHR Foundation that it said it planned to use to support commercialization of the assay, which it previously called APTUS-Aβ.
The company is pursuing FDA 510(k) clearance for the test, which received breakthrough designation from the agency in 2019.
According to C2N, PrecivityAD is the first in a series of blood-based assays the company is developing to improve the ability to diagnose and monitor the progression of Alzheimer's. The company and its collaborators at Washington University in St. Louis have also identified several other blood-based markers that could prove clinical useful, including p-tau181 and p-tau217. In studies published this summer, researchers including Wash U neurology professor Randall Bateman, a founder of C2N, found that plasma levels of p-tau217 correlated with p-tau217 levels in CSF, a notable result given that previous studies have found CSF p-tau217 levels are able to detect the Alzheimer's as much as 20 years before the onset of symptoms and shortly after the initial development of amyloid plaques in the brain.
A number of other groups are also exploring blood-based Alzheimer's markers. Last year, researchers at IBM identified a plasma protein signature predictive of CSF Aβ42 levels. Also last year, a team led by researchers at King's College London identified a panel of 12 blood proteins that could distinguish between asymptomatic subjects with high and low levels of brain Aβ deposits with a sensitivity of .78 and specificity of .77. In 2018, researchers at Japan's Center for Development of Advanced Medicine for Dementia identified a series of Aβ precursors and variants measured using immunoprecipitation combined with MALDI-TOF mass spec that could help detect and monitor Alzheimer's disease.
In addition to marking an advance in Alzheimer's diagnostics, PrecivityAD represents another notch on the still small but growing list of diagnostic companies offering multiplexed protein tests run on LC-MS/MS. Despite improvements in mass spec workflows and instrumentation, only a few tests using the technology for protein measurement have made it to the clinic, with Sera Prognostic's PreTRM test for preterm delivery and Biodesix's Nodify XL2 test for assessing lung nodules detected via computed tomography among the most prominent.