FDA Grants Alzheimer Biomarker Test Breakthrough Status

Roland Diggelmann, CEO of Roche Diagnostics

Roland Diggelmann

The FDA has granted a Breakthrough Device Designation to the Elecsys beta-Amyloid (1-42) and Elecsys Phospho-Tau (181P) cerebrospinal fluid assays, which can be used in the diagnosis of Alzheimer disease.

The diagnostic immunoassays measure the beta-Amyloid (1-42) and Phospho-Tau concentrations in cerebrospinal fluid (CSF) in adult patients with cognitive impairment who are being evaluated for Alzheimer disease or other causes of dementia. The assays are intended to help diagnose Alzheimer disease as opposed to age-related memory disorders through the use of biomarkers associated with Alzheimer disease.

The Elecsys beta-Amyloid (1-42) CSF, Elecsys Phospho-Tau (181p) CSF, and Elecsys(R) Total-Tau CSF immunoassays are currently approved in countries accepting the CE Mark. Voluntary participation in the Breakthrough Device Program will help expedite the development and FDA review of the CSF assays.

"We are excited about FDA's recognition of the potential clinical benefit the Elecsys CSF assays can bring to clinicians, laboratories, and their patients in diagnosing AD at an early stage," Roland Diggelmann, CEO of Roche Diagnostics, the company developing the test, said in a statement. “Roche was one of the first companies to use biomarkers in clinical trials and we will continue to explore high-performing diagnostic and disease-monitoring solutions.”

Earlier this year, the FDA announced a draft guideline to help advance the development of novel treatments for neurological conditions, through a modernization of the FDA's review process. As part of this decision, the agency noted that symptoms and progression of diseases, like Alzheimer, can go unchecked for years, placing emphasis on proper diagnosis.

"The FDA has been working closely with patients and the scientific community to gain the knowledge that will support intervention in very early Alzheimer disease in ways that have the potential to stop the disease before it causes clinical problems," FDA Commissioner Scott Gottlieb, MD, said in a statement.

"[The FDA's Draft Guidance for Industry: Early Alzheimer’s Disease: Developing Drugs for Treatment describes innovative approaches to studying very early disease before the onset of dementia, including strategies for trials incorporating patients with Alzheimer’s who haven’t experienced any visible impairment (in the form of cognitive or functional deficits), but who may be identified through the use of sensitive cognitive screening, imaging tests, or biomarkers," he said.

However, despite this push for better diagnostics and treatment, research done by Shana Stites, PsyD, at the Perelman School of Medicine, University of Pennsylvania, highlighted distinct stigmas that exist for patients with Alzheimer disease, which have led to many denying a diagnosis. This also highlights potential pitfalls of biomarker-based information about Alzheimer disease.

"These are important topics for clinicians to talk about with their patients who either have or are concerned about an Alzheimer diagnosis," said Stites. "By understanding what the biggest concerns are about the disease, we can help develop programs and policies to reduce the stigma about Alzheimer disease."

In their research, a sample of 317 adults with a median age of 49 years read and reacted to a fictional vignette of a person with Alzheimer disease dementia. The study randomly assigned participants to 1 of 3 groups for comparison. These groups were based on whether participants were told the person’s condition would worsen, improve, or remain unchanged.

In analyses adjusted for differences between the 3 study groups, over half of participants expected a person with Alzheimer disease dementia would be discriminated against by employers (55.3%; 95% CI, 47.0-65.2) and would be excluded from medical decision-making (55.3%; 95% CI, 46.9-65.4). Many also expressed concern that the person would have healthcare insurance limited because of data in the medical record (46.6%; 95% CI, 38.0—57.2) or have his healthcare insurance limited due to a brain imaging result (45.6%; 95% CI, 37.0–56.3).

The most common beliefs were expecting that the person would not remember most recent events (73.8%), would face employment discrimination (55.3%), and would be excluded from medical decision-making (55.3%).

"The Genetic Information Nondiscrimination Act of 2008 (GINA) helps to protect against discrimination on the basis of genetic data so this may offer assurance and protection to those who learn their genetic risk of Alzheimer's," said Stites. "But currently there are no policies to offer similar protections for individuals on the basis of a biomarker result. In addition to policies, like GINA, there's a need for programs to educate the public about those policies. In our study, 45% of those surveyed were worried a genetic result could lead to insurance-based discrimination even though this study was conducted years after GINA was created."