Roche Gets FDA Clearance for CSF Beta-Amyloid and Phospho-Tau Alzheimer Disease Assays

Thomas Schinecker, PhD

According to an announcement from Roche, the company’s Alzheimer disease (AD) cerebrospinal fluid Elecsys assays—including beta-amyloid1-42 CSF II (Abeta42) and phospho-Tau181P (pTau181)—have been approved by the FDA for use with the cobas fully automated immunoassay analyzers.¹

The biomarkers are hallmarks of AD pathology, and the assays utilize their ratio (pTau181/Abeta42), which are in line with a negative beta‑amyloid PET scan if the result is less than or equal to the cutoff (negative) and with a positive beta‑amyloid PET scan if the result is above the ratio cutoff (positive). Roche noted in the announcement that its AD assays “achieve 90% concordance” with amyloid PET scans.

In an analytical performance, reproducibility, method comparison with commercially available assays, investigators noted that the Elecsys pTau181 CSF assay, “demonstrated good correlation with commercially available tau assays,” showing high sensitivity (limit of quantitation, 4 pg/mL) and linearity over the measuring range (8-120 pg/mL), which covering the entire concentration range. Lot-to-lot and platform comparability demonstrated good consistency (Pearson r, 1.000).²

Similarly, the Elecsys Abesta42 assay showed high correlation with the Innotest β-amyloid1-42 (Spearman ρ, 0.954), Inno-Bia AlzBio3 (Spearman ρ, 0.864), and ADx-Euroimmun ß-amyloid1-42 ELISA (Pearson r, 0.925). Compared with liquid chromatography-tandem mass spectrometry measurements, the Elecsys assay reported a correlation with Roche Diagnostics- and University of Pennsylvania-developed methods (Pearson r, 0.949 and 0.943, respectively).³

Thomas Schinecker, PhD, CEO of Roche Diagnostics, said in a statement, “Globally, up to 75% of people living with Alzheimer’s disease have not been diagnosed, and those who have often report a long and complicated process. The Elecsys AD CSF assays have the potential to guide more people with suspected Alzheimer’s disease toward a diagnosis than ever before. As we are starting to see exciting results for new potential Alzheimer’s treatments, reliable tests that have been clinically validated will be critical in ensuring the right patients are identified and able to benefit from them.”¹

Roche noted in the announcement that the high costs of and limited availability and exposure to the radioactivity of PET scan imaging limit its clinical utility, adding that the assays, which detect multiple markers without radiation in a single draw, offer “a more affordable and accessible routine option to confirm the presence of amyloid in the brain.”

Alireza Atri, MD, PhD, of the Banner Sun Health Research Institute, discussed the challenge of access to AD screening tools in a NeurologyLive® Insights series. He explained that when ordering PET scans or spinal fluid draws to look at the amyloid or tau involvement, “there are complexities because of coverage. But, in clinical practice, individuals who have atypical syndromes or early onset syndromes who want higher degrees of confidence regarding their diagnosis will end up going down the pathway of seeing specialists at that point to improve the level of confidence that their condition is actually caused by Alzheimer disease. In which case, then you have an option of spinal fluid analysis or the PET scans, which aren’t routinely covered by insurance companies.”

Additionally, in July 2022, the FDA granted breakthrough device designation to its Elecsys Amyloid Plasma Panel,⁴ a minimally invasive tool that enables the measurement of AD biomarkers from a blood sample. The decision was the first time an in-vitro diagnostics manufacturer received this designation for a blood-based AD biomarker test.

This news from Roche Diagnostics follows recently announced findings from the company’s therapeutic development in AD, the phase 3 GRADUATE 1 and 2 studies (NCT03444870; NCT03443973).⁵ Presented at the Clinical Trials on Alzheimer Disease (CTAD) meeting, the data showed that gantenerumab, a fully human monoclonal IgG1 antibody, did not meet its primary end points of slowing clinical decline in patients with early AD. All told, gantenerumab-treated patients demonstrated a slowing of clinical decline of –0.31 (P = .0954) and ­–0.19 (P = .2998) on Clinical Dementia Rating-Sum of Boxes scores in GRADUATE 1 and 2, respectively, which was not statistically significant. The assessment, which measured cognitive and functional change across 6 areas, showed a relative reduction of 8% in GRADUATE 1 and 6% in GRADUATE 2 compared with placebo.

REFERENCES
1. Roche Alzheimer’s disease Cerebrospinal Fluid (CSF) assays receive FDA clearance, supporting more accurate and timely diagnosis. News release. Roche. July 19, 2022. Accessed December 9, 2022. https://diagnostics.roche.com/us/en/news-listing/2022/roche-alzheimers-disease-cerebrospinal-fluid-assays-receive-fda-clearance.html
2. Lifke V, Kollmorgen G, Manuilova E, et al. Elecsys® Total-Tau and Phospho-Tau (181P) CSF assays: Analytical performance of the novel, fully automated immunoassays for quantification of tau proteins in human cerebrospinal fluid. Clin Biochem. 2019;72:30-38. doi:10.1016/j.clinbiochem.2019.05.005
3. Shaw LM, Hansson O, Manuilova E, et al. Method comparison study of the Elecsys® β-Amyloid (1-42) CSF assay versus comparator assays and LC-MS/MS. Clin Biochem. 2019;72:7-14. doi:10.1016/j.clinbiochem.2019.05.006
4. Roche's Elecsys Amyloid Plasma Panel Granted FDA Breakthrough Device Designation to Enable a Timely Diagnosis of Alzheimer’s Disease. News release. Roche. July 19, 2022. Accessed December 9, 2022. https://diagnostics.roche.com/us/en/news-listing/2022/elecsys-amyloid-plasma-panel-fda-breakthrough-device-designation-alzheimers.html
5. Genentech provides update on phase III GRADUATE program evaluating gantenerumab in early Alzheimer’s disease. November 13, 2022. Accessed December 9, 2022. https://www.gene.com/media/press-releases/14974/2022-11-13/genentech-provides-update-on-phase-iii-g