​One of EPND's goals is to support the regulatory qualification of biomarkers for neurodegenerative diseases. Biomarker qualification ensures that biomarkers are reliable, reproducible, and clinically meaningful for diagnosing and monitoring neurodegenerative diseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and Dementia with Lewy Bodies (DLB).

Audrey Hermans is currently in the third year of her PhD studies, which are being completed as part of the EPND programme. Andrey works at the Dutch Medicines Evaluation Board (CBG-MEB) the National Competent Authority for the Netherlands, where she is studying how biomarkers are evaluated and approved by regulators, aiming to identify potential obstacles that could hinder biomarker qualification, and create guidance to support developers.

Audrey will be presenting her work at the 2025 AD PD conference, taking place in Vienna between 1-5 April. To find out more, we spoke to Audrey, who shared some of her key findings, as well as her views on how EPND can help advance biomarker development and approval.

What is the background to your research and what was the research question you were trying to answer?

We know that biomarkers are powerful tools to facilitate early diagnosis of different types of diseases including the neurodegenerative diseases. And we know that biomarkers can help with improving patient selection and stratification, and understanding whether a therapy is working or whether it's safe. But there was not really a detailed overview of how biomarkers were used in the field of neurodegenerative diseases in regulatory processes, or for regulatory decision making.

This is what we set out to do in the study we are presenting at AD/PD. In our study, we analysed marketing authorisation applications, qualification and scientific advice procedures regarding neurodegenerative diseases. We explored the extent to which the biomarkers are used in the regulatory development of treatments for neurodegenerative diseases. We also wanted to learn about the topics that were discussed during regulatory advice and decision-making processes. And then we wanted to understand whether or not shared data related to biomarkers was being used in regulatory processes.

How are biomarkers regulated and approved in Europe?

In 2008, the European Medicines Agency (EMA) launched the “qualification of novel methodologies” pathway, which provides a route for tools such as biomarkers to be assessed and, potentially, receive endorsement by the EMA. This pathway can result in a qualification opinion, advice, or letter of support from the Committee for Human Medicinal Products (CHMP).

A qualification opinion means that the EMA endorses the biomarker’s relevance and accuracy, which means that it has proven utility for its use as, for example, a diagnostic tool, or a tool to measure disease progression, in the context of research and development. Alternatively, the CHMP can provide a qualification advice, which identifies specific developments that will be required in order to achieve a qualification opinion. Or the CHMP may provide a Letter of Support, which indicates that the methodology is very promising, but is not yet ready to seek a formal advice or opinion. Qualification opinions and Letters of Support are made publicly available, wheras qualification advices are kept confidential.

In our analysis, we looked at all these qualification documents, together with scientific advices and the marketing authorisations that were submitted to the EMA, to understand the current regulatory state of play regarding biomarkers for neurodegenerative diseases.

What were your main findings?

First of all, we saw that some biomarkers have established roles in certain disease areas. For example, for multiple sclerosis, we saw that biomarkers were already incorporated in guidelines and several regulatory processes. However, overall we saw that more precise and reliable biomarkers are necessary, especially to improve diagnostic accuracy and treatment monitoring for neurodegenerative diseases.

When we analysed the regulatory documents, we saw that a robust evidence base is very important for biomarker qualification and for the development of new treatments. Companies need to show the biological plausability of biomarkers, and that there are clear clinical benefits for measuring them. On the data front, we noted that data sharing among stakeholders is really vital: it helps generate evidence and enhances our understanding of neurodegenerative diseases.

What disease areas did you focus in in on in your research and did you see any differences between the areas?

We looked at a very long list of diseases! We looked at the ICD 11 to understand which diseases were classified as neurodegenerative diseases, and searched for procedures in these areas – 27 diseases in total. The diseases for which we saw the most procedures by far multiple sclerosis, Alzheimer's disease and Parkinson's disease. However, we did find a few regulatory processes for biomarkers of ALS, Huntington's disease and other rarer neurodegenerative disorders.

For Alzheimer's disease (AD), we saw that there were many different biomarkers in the regulatory documents we analysed. But we also realised during our work that there are biomarkers in AD and PD that are not yet being used or assessed in regulatory processes, for example blood based biomarkers. We know that there is a growing body of evidence supporting their clinical use, but are still waiting to see them advancing through the regulatory pipeline.

It was interesting to see that certain biomarker developers used publicly-available neurodegeneration datasets such as ADNI or PPMI – showing how data sharing can really aid in the development and regulatory validation of biomarkers.

Audrey Hermans, CBG-MEB, the Netherlands

When it comes to Parkinson's disease (PD), we did not find many advices, opinions or letters of support, but that may be due to the exclusion of performance outcomes and digital biomarkers, which are a very large area of biomarker research in PD.

How is EPND helping to advance biomarker science and qualification?

EPND’s main purpose is to accelerate data and biosample sharing. Biosample sharing is crucial for the development of accurate, reliable biomarkers, as it enables us to broaden our understanding of how they reflect disease-related changes in the general population. In our analysis, we made some interesting observations relating to data sharing. Specifically, we saw that some applicants made use of publicly-available neurodegenerative disease datasets, such as the Alzheimer’s Disease Neuroimaging Initiative (ADNI) or Parkinson’s Progression Markers Initiative (PPMI) – showing how data sharing can really aid in the development and regulatory validation of biomarkers.

What makes EPND special for you?

EPND brings together a very diverse group of partner organisations and colleagues, which makes it a really special project to work in! Within the different workstreams, there are people from a range of backgrounds and research areas - but we all come together to have this ultimate purpose of making data and biosamples available, so we can help people living with neurodegenerative diseases.

Many thanks to Audrey and colleagues for all their work! Download Audrey's poster by clicking on the button below: