The European Medicines Agency (EMA) has announced its intention to revise its guideline on the clinical development of Alzheimer’s disease (AD) treatments. The proposed update reflects both recent scientific advancements and lessons learned from new Alzheimer’s drug approvals and marketing authorization applications (MAAs), including the recent approval of Leqembi in the European Union.
This move signals a shift in how regulators may evaluate clinical trials for Alzheimer’s therapies, especially with the emergence of novel biomarkers and evolving diagnostic frameworks.
A Growing Public Health Priority
Dementia continues to pose a significant healthcare challenge in Europe, and Alzheimer’s disease remains the most common form, accounting for 60 to 80 percent of cases. Despite this burden, treatment options remain limited. No therapy has yet been shown to halt disease progression.
Since its initial guideline in February 2018, EMA has seen several critical changes in the field. These include updated definitions of AD, increased understanding of disease stages, and advancements in diagnostics that now rely more heavily on biological markers.
Toward a New Model for AD Diagnosis
One of the key motivations for the guideline update is the shift toward a biological model for diagnosing Alzheimer’s. EMA notes that the current definition of AD is evolving away from a clinical-biological framework and toward a purely biological model supported by biomarkers.
While this model has strong research support, it is not yet fully aligned with clinical practice, especially regarding patients in the asymptomatic phase. EMA acknowledges the need to carefully address these discrepancies in the updated guideline, ensuring both scientific accuracy and clinical applicability.
The agency also points to growing interest in plasma biomarkers, which may support not only research but also future clinical use in diagnosing Alzheimer’s and tracking disease progression.
Implications for Clinical Trial Design
EMA’s updated guideline will provide direction on several aspects of trial design and regulatory planning:
- Refined diagnostic criteria will impact how sponsors define their study populations and set eligibility criteria.
- Endpoint selection is a key area of focus, particularly in early-stage AD trials where traditional scales are not always appropriate.
- Biomarker use will be addressed in greater detail, including how biomarkers can be used for patient selection, enrichment strategies, and monitoring treatment response.
The agency also emphasizes the importance of long-term safety and efficacy data, drawing from its recent experience reviewing anti-amyloid therapies like Leqembi. Regulators expect Alzheimer’s therapies to demonstrate meaningful and sustained benefits, particularly as they move into earlier disease stages and asymptomatic populations.
Timeline and Development Process
The EMA’s Central Nervous System Working Party (CNSWP) will lead the development of the updated draft, with input from the Methodological Working Party (MWP), the Scientific Advice Working Party (SAWP), and other relevant groups.
A draft guideline is expected to be released for public consultation in the fourth quarter of 2026. Stakeholders will have until February 28, 2026, to submit comments through the EMA’s EUSurvey platform.
Strategic Takeaways for Developers
This upcoming revision has important implications for drug developers working in the Alzheimer’s space. Companies should begin reviewing their clinical development strategies to ensure alignment with the anticipated changes, particularly around eligibility criteria, endpoints, and the integration of biomarkers.
At EMMA International, we help life science companies navigate shifting global regulatory expectations. Whether your team is planning a new Alzheimer’s trial or preparing for MAA submission in the EU, our experts can support clinical strategy, scientific advice preparation, and regulatory document development.
For more information on how EMMA International can assist, visit www.emmainternational.com. Contact EMMA International at (248) 987-4497 or by email at info@emmainternational.com to learn more.
References
Eglovitch, J. (2025, August 6). EMA proposes updating guideline for Alzheimer’s disease treatments. Regulatory News.
