NEW YORK ─ Italian startup Diadem is preparing to launch a blood test in the third quarter of this year for clinicians seeking a screening tool to detect Alzheimer's disease in patients with few or no symptoms.
The test, AlzoSure Predict, uses a proprietary antibody and laboratory-based mass spectrometry to target a conformational variant of the p53 protein, called U-p53AZ, that reflects the production of amyloid beta in the brain.
Unlike other in vitro diagnostic tests that are being developed to detect Alzheimer's disease in symptomatic patients, AlzoSure Predict can identify patients with few or no cognitive symptoms who will decline to Alzheimer's disease up to six years before diagnosis, said Diadem CEO Paul Kinnon.
"Our clinical validation data also show that the blood test has better performance than other biomarkers of Alzheimer's disease such as tau and amyloid beta and can differentiate individuals progressing to Alzheimer's disease from those experiencing other types of dementia," Kinnon said.
The company, launched in 2012 as a spinout from the University of Brescia, recently announced the receipt of a €7.5 million ($8.2 million) loan, as well as CE marking and US Food and Drug Administration breakthrough device designation for AlzoSure Predict.
It is planning a Q3 launch of a kit in Europe and a laboratory-developed test from a CLIA-certified laboratory in an undisclosed location in the US, Kinnon said.
The CE marking "proves we have a robust test that has been through validation" and the European grant "will allow us to expand the development of the product and technology in the coming years and support our commercial activities," Kinnon said.
In preparation for the launch of AlzoSure Predict, Diadem is in discussions with a few undisclosed firms that have laboratory networks throughout Europe including in Germany, Poland, France, Italy, Spain, and the UK, Kinnon said, adding that the company will provide kits with reagents and the laboratories will become its distributors.
If the company can obtain FDA 510(k) clearance, it also anticipates offering a kit for sale by US laboratories within the next two years, which would augment the nearer-term availability of AlzoSure Predict from the CLIA-certified laboratory, Kinnon said. The firm is also working on a version of AlzoSure Predict to run on laboratory ELISA systems when mass spec instruments are not available.
With an eye on its future product pipeline, Diadem is also developing new tests, and last week reported early validation data for an assay called AlzoSure Confirm at the AD/PD 2022 International Conference on Alzheimer's and Parkinson’s Diseases in Barcelona.
Unlike AlzoSure Predict, which is prognostic, AlzoSure Confirm uses seven antibody biomarkers that are derivatives of U-p53AZ along with mass spectrometry to detect current Alzheimer's disease in patient blood, Kinnon said.
For the clinical study described in Barcelona, the firm used a subset of 500 samples from patients exhibiting different stages of cognitive decline to investigate the full sequence of post-translational modifications (PTMs) of U-p53AZover the course of a continuum that culminates in Alzheimer's disease.
The resulting PTM fingerprints, or signatures, are characteristic of different stages of the progression to Alzheimer's, and in the study, the PTM signatures reliably detected patients with Alzheimer's as determined by standard clinical diagnostic methods and distinguished them from patients with other dementias, the firm said.
Diadem is not yet disclosing potential launch dates for AlzoSure Confirm.
Since it emerged from stealth mode with the appointment of Kinnon as its CEO in 2020, the firm has been validating its flagship AlzoSure Predict.
Last October, it presented data at the 22nd International Conference on Alzheimer’s Drug Discovery from a 482-patient longitudinal study, which was also published as a MedRxiv preprint last August.
The study showed that AlzoSure Predict detects cognitive decline that leads to Alzheimer's disease with an area under the receiver operating characteristic curve (AUC) of greater than 90 percent regardless of the cognitive status of patients at the time of the test, and can determine the classification of the patient’s stage of dementia with an AUC of greater than 95 percent.
Diadem said the study will soon be published in the Journal of Prevention of Alzheimer's Disease.
Last November, the firm presented data from the same 482-patient study at the 14th Clinical Trials on Alzheimer’s Disease meeting in Boston that suggested AlzoSure Predict can play a role in facilitating and accelerating clinical trials for new therapeutic candidates to treat Alzheimer's.
Diadem is entering a space that numerous diagnostic test developers hope to soon occupy.
Fujirebio is pursuing FDA clearance for its CSF-based Alzheimer's disease diagnostic test for which it received FDA breakthrough device designation in 2019, and Roche is developing two CSF-based immunoassays for its Elecsys system for which it obtained breakthrough device designation in 2018.
Meanwhile, C2N Diagnostics launched its PrecivityAD blood test as a lab-developed test in 2020, and last year, the FDA granted breakthrough device designation to Quanterix for its Simoa phospho-Tau 181 (pTau-181) blood test for Alzheimer's disease.
In a research note last week, BTIG analyst Sung Ji Nam said the investment bank is "more positive than before" on Quanterix's competitive position based in part on its development of the blood-based diagnostic test.
If neurodegenerative disease therapies currently in the late stages of development are successful, they could "markedly accelerate and expand diagnostic opportunities in [neurodegenerative diseases]," she said.
The most important effect of Diadem's validation studies and recent CE marking may be that the test will be available for screening while more treatments appear poised for FDA approval, said James Matthew Voci, director of neurology at Amita Health Saint Francis Hospital in Evanston, Illinois.
"We expect a number of effective monoclonal therapies to enter the market in the next few years that target the abnormal proteins that form during Alzheimer's disease," Voci said, adding that FDA-approved aducanumab (Biogen's Aduhelm), which targets amyloid build-up in the brain, is a "breakthrough, landmark drug" that can drive an increase in testing. The agency approved aducanumab last June as an amyloid beta-directed antibody treatment for Alzheimer's.
Voci, a practicing neurologist, is familiar with AlzoSure Predict and its validation studies but he is not affiliated with Diadem.
Currently, individuals who start exhibiting Alzheimer's symptoms are usually referred to a neurologist "but by then brain damage has progressed," he said, adding that the availability of noninvasive tests for early detection would enable early treatment with the potential for better patient outcomes.
Though other in vitro diagnostic tests that use CSF or blood samples are in development, "none are broadly available or have data on pre-symptomatic sensitivity," Voci said.
Further, positron emission tomography imaging, the current gold standard for detecting Alzheimer's disease, is not broadly available, lacks sensitivity for early detection, and is prohibitively expensive for many, highlighting the need for affordable screening tests, he said.
Diadem said it expects the price for its prognostic test will be in the range of $500 to $1,000 and added that it intends to pursue reimbursement from payors.
One of the firm's most important objectives may become its greatest commercial challenge, Voci said. The firm will need to persuade primary care physicians "that the test needs to be part of an annual screening assessment" for patients of a certain age, possibly 50 or older, he added.