p-Tau217 Emerges as a Leading Blood-Based Biomarker for Alzheimer’s Disease Amid FDA Breakthrough Designations and Industry-Wide Commercialization

We have discussed that in January last year, the Alzheimer's drug Leqembi was approved by the FDA through an accelerated pathway, finally providing a treatment option for Alzheimer’s disease. As a result, 2023 became a breakthrough year for blood tests for Alzheimer’s disease (see article for reference)."Roche and Quest Are Watching Closely: Is This the Year of the Big Breakthrough for Alzheimer's Blood Tests?"）。

And this year, the Alzheimer's blood test continues to enter a feverish stage. This Thursday (4/11),Roche Announces FDA Breakthrough Device Designation for Elecsys pTau-217 Plasma Biomarker Test。

This test also marks the first FDA Breakthrough Device Designation for Roche and Eli Lilly since their collaboration began in March 2023. The last time Roche received this designation from the FDA was in 2022 for the Elecsys pTau-181 and ApoE4 immunoassays. Currently, Roche has two other FDA-approved tests: the Elecsys beta-Amyloid (1-42) CSF II (Abeta42) and the Elecsys Total-Tau CSF (tTau) assays. Both tests analyze cerebrospinal fluid, a sampling method that is more complex and more painful for patients.

Regarding ptau-217, it seems to have recently become a very popular biomarker for Alzheimer's disease.Just the day before yesterday, Quanterix CEO Masoud Toloue said that ptau-217 as a marker for Alzheimer's disease is gaining momentum.Prompting Quanterix to decide to protect its intellectual property(Patent No.: 11275092). Quanterix's research on ptau-217 was also conducted in collaboration with Eli Lilly.

However, the biomarker pTau-217 has long been utilized and commercialized by multiple testing companies. Aside from Roche,Companies like LabCorp, Neurocode, and C2N Diagnostics have already launched their blood ptau-217 tests, and Quest has also announced that it will introduce a plasma pTau-217 test in the second half of this year.。

Why Is pTau-217 Now a Hot Biomarker for Alzheimer’s Disease?

The mainstream biomarkers for Alzheimer's disease blood tests currently include: Aβ42/40, pTau-181, pTau-217, and pTau-231.

Aβ42/40: Although Roche has commercialized a test for detecting Aβ42/40 in cerebrospinal fluid, Aβ (beta-amyloid) in the blood is still difficult to detect. Aβ is also produced peripherally, but its concentration does not accurately reflect the accumulation of amyloid protein within the central nervous system. Despite Quest’s AD-Detect, launched in July last year, also using Aβ42/40 from blood, there are no peer-reviewed publications on this method, thus lacking validation or clear interpretive value; as a result, the test was discontinued last month.

pTau-181, ptau-217, and pTau-231: Currently, more than 80 ptau are being studied, among which ptau-217 and pTau-181 are considered the most promising biomarkers, while pTau-231 can be used as a state marker, but this still needs to be verified. In a prospective study cohort, compared with plasma pTau-181, pTau-231, N-terminal tau, GFAP or NfL,p-tau217 shows a stronger correlation with aβ positivity(Mattsson-Carlgren et al., 2024). In addition, preliminary evidence suggests that,Ptau-217 levels increase during the preclinical stage of Alzheimer's disease and are associated with Aβ burden in the brain.(Gonzalez-Ortiz et al., 2023). Both pTau-181 and ptau-217 performed well in distinguishing between types of neurodegenerative disease lesions.But in distinguishing Alzheimer's disease from other forms of neurodegenerative diseases, pTau-181 seems to be less accurate than ptau-217.（Thijssen et al., 2021）。

Interestingly, a study initiated by the Global Biomarker Standardization Consortium (GBSC) compared various ptau-217 assays from 11 different manufacturers. Despite the small sample size of the experiment, it was found that p-tau217 had a higher AUC than p-tau181 and p-tau231. This also brought relief to experts in the field, as it indicates that there are multiple relatively reliable plasma p-tau217 tests.

We return to Quanterix's earlier intention to patent ptau-217. Arti Rai, a law professor at Duke University and an intellectual property expert, mentioned the quantification levels of tau protein.Establishment of Patent Infringement ClaimsIt will be challenging because this is similar to a law of nature, which cannot be patented, but the method for laboratory testing can be patented.

▲QuanterixPatent 11275092

In this case, it may have an impact on Roche, Labcorp, and Quest, but not on companies like C2N, becauseC2N is detected by mass spectrometry.If Quanterix really picks up the weapon of patents and touches the cake of these big companies, the road to patent protection may not be so easy. After all, Alzheimer's detection is a battleground for all players at present.