Roche Diagnostics Guides New Alzheimer's Test Through Trials
A conversation with Maria-Magdelena Patru, MD, PhD, Medical and Scientific Affairs, Roche Diagnostics
A little over 10 percent of people age 65 and the older in the U.S. are living with Alzheimer’s dementia, according to the Alzheimer’s Association annual report from 2024. Crucial to its early diagnosis and treatment are suitable diagnosis methods, which are currently combinative and include medical histories, lab tests, and brain imaging. But blood tests like the Elecsys pTau181 plasma test developed by Roche Diagnostics are poised to strengthen early detection and risk assessment. Roche Diagnostics’ Maria-Magdelena Patru, MD, PhD discusses the test and how they’re approaching its clinical trials.
What problem is the Elecsys pTau181 plasma test addressing or challenge is it solving when it comes to diagnosing Alzheimer’s disease?
Today, barriers to early and accurate diagnosis of Alzheimer’s disease exist across the globe, with up to 75% of people living with dementia without a causal diagnosis. Those who have received a diagnosis waited, on average, 2.8 years after symptom onset to seek one. To address the growing strain that Alzheimer’s disease is putting on healthcare systems, it will be essential to diagnose it in early symptomatic disease stages (i.e., mild cognitive impairment and mild dementia) and treat those patients with amyloid-targeting therapies before they transition to moderate or severe dementia. That can be achieved by providing testing tools for clinicians that identify disease-specific pathology and by increasing patients’ awareness and access to these tests.
Early disease-stage diagnosis will facilitate access to the amyloid-targeting as well as other new disease-specific therapies, as they become available. Currently, the FDA-approved/cleared tests such as the cerebrospinal fluid ratios and amyloid Positron Emission Tomography (PET) are able to confirm amyloid pathology and can be used to qualify patients for the amyloid-targeting therapy in early disease stages. However, access to these tests is limited and their invasiveness is higher compared to a blood draw. The Elecsys pTau181 blood test (currently in development) could transform Alzheimer’s disease patients’ pathways because a blood test is minimally invasive and scalable. It is designed with the intent to rule out patients with a low likelihood of amyloid pathology in individuals under evaluation for cognitive decline, therefore reducing the number of patients in need of further assessment for Alzheimer’s. Once approved, the test is meant to be used in addition to other clinical investigations and/or tests and interpreted in the clinical context. We expect that the clinical implementation of this test will accelerate the path to diagnosis and management of individuals with cognitive impairment.
Clinical research conversations about patient enrollment often contain the popular refrain that trial participants must reflect the patient population of the investigational drug or device it intends to serve. How has Roche done that with this trial, and why is that important?
A clinical trial representative of the real-world population can be challenging to accomplish, but the effort is worthwhile, as it promotes health equity and defines good science.
To validate the pTau181 test, we conducted a prospective, multicenter study, enrolling individuals with cognitive symptoms at sites across the U.S. and Europe. We intended to have a comprehensive study population from the gender, age, racial, and comorbidities perspectives, reflective as much as possible of the real-world population for which the test is intended. This is important because any of these factors could affect the blood proteins/biomarkers measured with laboratory tests and cause changes in their levels which can, in some cases, be significant enough to impact clinical decisions. Therefore, in addition to a comprehensive clinical validation for the test, we recommend that HCPs interpret the results in the context of all other clinical information.
How did you identify the appropriate number and type of participants to yield statistically significant and clinically compelling results?
Once the study objectives and eligibility criteria for the intended use population were outlined, we used statistical analyses methods to determine the appropriate size of the population needed to achieve study goals. Then we specifically searched for sites situated in various geographical locations and settings, with the appropriate infrastructure and experience and ability to enroll our target population.
How can this in vitro diagnostic test, if approved, become part of standard-of-care, demand widespread adoption, and ultimately gain reimbursement?
When implemented in clinical practice for patients with cognitive symptoms, this test could have an important role in shaping and streamlining the diagnostic pathway and contributing to, in addition to other clinical investigations, the timely identification of Alzheimer’s, in the early disease stage. We envision this assay to be part of a comprehensive and targeted diagnostic workup, reducing costs for the healthcare system by minimizing expensive and invasive diagnostic procedures and by reducing unnecessary procedures for patients with low likelihood of amyloid pathology. Additional clinical utility studies are expected to demonstrate the positive impact on clinicians’ decisions and the benefit for patients.
Given the novelty of this test, if approved, what are the considerations for introducing it to clinicians? What might they want to learn about it and its role in their treatment decision?
There is a significant need to increase HCPs’ depth of knowledge on the recent testing and therapy developments in Alzheimer’s. The field of neurology is fast-paced, and it is the responsibility of all involved (e.g., industry, academia, and dementia experts) to facilitate educational activities for HCPs, laboratories, but also for the communities. HCPs will need to understand a test's intended use but also its limitations, as well as its performance and how the performance can vary with the prevalence of the disease. It also will be important to have a good understanding of the result interpretation and be able to explain the implications of that result to patients and follow up with the appropriate next steps, such as additional clinical investigations and/or referral to a specialist.
What lessons did you learn or best practices did you develop as you planned for and executed this clinical trial?
In conducting these types of clinical trials, we always follow the Good Clinical Practice principle, which incorporates ethical and scientific quality standards. In addition, to ensure that our study design answers not only clinical but also specific regulatory requirements, during development we request feedback from the FDA through their formal pre-submission program. Interacting with clinicians and researchers early in the process helps tremendously with the study design and protocol. Site training to ensure protocol compliance on the study protocol is also an essential part of the process. Equally important is documentation, which in itself requires significant planning and resources.
Lastly, I would like to single out one main factor that ensures the success of such a complex trial: internal and external partnership. We are very grateful to all our colleagues who have been working on this development project for years but also to all the sites’ personnel and investigators who helped us with this clinical trial, as well as all the participants, whose contribution is invaluable in the advancement of this test.
About The Expert:
Maria-Magdalena Patru, MD, PhD, is an experienced physician-scientist, with over 15 years in the field and more than 11 years in the in-vitro diagnostics (IVD) industry. Currently serving as the scientific partner for neurology at Roche Diagnostics US, she leads a team developing medical strategies for neurology biomarkers, primarily focusing on Alzheimer’s. Her background includes a medical degree, laboratory medicine training, a Ph.D. in microbiology and immunology, a clinical laboratory fellowship, and extensive experience in medical and scientific affairs, particularly in IVD product development, validation, and clinical trials.