Biomarkers for neurodegenerative diseases in regulatory decision-making by the European Medicines Agency.
Biomarkers for neurodegenerative diseases in regulatory decision-making by the European Medicines Agency.
Where did the research take place?
The study site has not been established. Author addresses may differ from where the research occurred.
Utrecht, NL · Author affiliation
Dutch Medicines Evaluation Board (MEB) Utrecht The Netherlands.Location evidence
Groningen, NL · Author affiliation
Department of Clinical Pharmacy and Pharmacology, University Medical Centre Groningen University of Groningen Groningen The Netherlands.Location evidence
Amsterdam, NL · Author affiliation
European Medicines Agency Amsterdam The Netherlands.Location evidence
Maastricht, NL · Author affiliation
Mental Health and Neuroscience Research Institute Maastricht University Maastricht The Netherlands.Location evidence
Luxembourg, LU · Author affiliation
Alzheimer Europe Luxembourg Ville Luxembourg.Location evidence
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Original abstract
IntroductionBiomarkers (BMs) are valuable tools to facilitate early diagnosis of (subtypes of) diseases, improve patient selection and stratification, and detect therapeutic effects or safety concerns. This study explores the extent to which BMs are utilized in the development of treatments for neurodegenerative diseases (NDDs), as well as topics of discussion regarding BMs in regulatory advice- and decision-making processes and sharing of BM-related data.MethodsThe European Medicines Agency's marketing authorization application (MAA), qualification (QA/QO), and scientific advice (SA) procedures regarding NDDs were screened, and those that mention BMs were analyzed. Data were extracted on the intended disease, BM type, and context of use proposed by applicants. BMs were categorized based on both nature and function.ResultsIn total, 105 procedures that discussed BMs were analyzed, 57 SAs (January 2020 to December 2022), 19 QAs/QOs (January 2008 to December 2023), and 29 MAAs (January 1995 to December 2023). The majority involved Alzheimer's disease (AD; n = 30), Parkinson's disease (PD; n = 9), and multiple sclerosis (MS; n = 33). Imaging BMs were the most common type of BMs discussed, and most BMs were used as pharmacodynamic/response measures. The acceptance and role of BMs differed between AD, PD, MS, and other NDDs. In regulatory procedures for AD, for example, diagnostic BMs guiding patient selection were commonly discussed, whereas in MAAs for MS, imaging BMs (particularly lesions) were generally accepted as supportive/secondary endpoints.DiscussionDespite the established role of certain BMs, mainly imaging BMs for MS, there remains a major need for more precise and reliable BMs to improve diagnostic accuracy and treatment monitoring for NDDs. To implement novel BMs and facilitate development of new treatments and to eventually improve clinical practice, robust evidence bases showcasing biological plausibility or clear clinical benefits are essential. Collaboration and data-sharing among stakeholders is vital in generating this evidence and enhancing the understanding and management of NDDs.HighlightsThe European Medicines Agency's marketing authorization applications and qualification and scientific advice procedures.One hundred five procedures were analyzed regarding neurodegenerative diseases that discuss biomarkers.We found that acceptance and role of biomarkers differ per disease.Biological plausibility/clinical benefits are essential for biomarker implementation.