Mapping the Current Landscape of Alzheimer’s Disease Drug Development: Trends, Challenges, and Future Directions


Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that primarily affects older adults leading to cognitive decline, behavioral changes, and ultimately loss of independence. It represents a significant global health burden with millions of people affected worldwide and numbers expected to rise dramatically due to the aging population. Despite extensive global medical research, effective therapies to prevent, delay, or halt the progression of AD remain elusive. The need for new treatments is urgent, driven by the increasing prevalence of the disease and its profound impact on individuals, families, and healthcare systems. Several challenges complicate the development of effective AD therapies, first, AD is characterized by multiple pathological processes, including amyloid-beta plaques, tau tangles, neuroinflammation, and synaptic dysfunction. Targeting these diverse and interconnected mechanisms is complex and requires multiple therapeutic approaches. Moreover, designing and conducting clinical trials for AD is inherently challenging and identifying appropriate endpoints, to ensure adequate trial duration, and to recruit sufficient participants are significant obstacles. Additionally, the variability in disease progression among individuals complicates the assessment of therapeutic efficacy. Furthermore, reliable biomarkers are essential for early diagnosis, patient stratification, and monitoring therapeutic responses. Unfortunately, the development and validation of biomarkers for AD are ongoing challenges. Additionally, the high costs and lengthy timelines associated with AD drug development pose economic challenges and the regulatory requirements for demonstrating efficacy and safety are stringent, adding to the complexity of bringing new therapies to market.

To this end, new paper published in Journal Alzheimer’s Dementia and led by Professor Jeffrey Cummings from the University of Nevada alongside Dr. Yadi Zhou, Dr. Garam Lee, Dr. Kate Zhong, Dr. Jorge Fonseca, and Professor Feixiong Cheng from Case Western Reserve University, the authors provided a comprehensive overview of the current state of AD drug development. They analyzed clinical trials registered on, categorized and quantified ongoing efforts in AD drug development. The researchers utilized the Common Alzheimer’s Disease Research Ontology (CADRO) to classify the therapeutic targets of the drugs under investigation. They also identified trends in therapeutic targets and approaches, noting shifts in focus areas compared to previous years.

The researchers first classified the trials based on their phases of development—Phase 1, Phase 2, and Phase 3. They identified a total of 164 trials assessing 127 drugs within the AD pipeline for 2024. The classification revealed that there were 48 trials in Phase 3 testing 32 drugs, 90 trials in Phase 2 assessing 81 drugs, and 26 trials in Phase 1 testing 25 agents. They observed that the distribution highlighted a robust mid-stage development focus, with nearly twice as many trials in Phase 2 as in Phase 3. This indicated a healthy pipeline of therapies transitioning from proof-of-concept to more extensive efficacy and safety testing. The presence of multiple Phase 1 trials suggests ongoing efforts to introduce new therapeutic candidates into the clinical landscape. They categorized the drugs into therapeutic categories based on CADRO. They found that 34% (56 trials) were disease-modifying biological agents, 41% (68 trials) were disease-modifying small molecule drugs, 10% (17 trials) were cognitive-enhancing agents, and 14% (23 trials) were drugs for treating neuropsychiatric symptoms. The authors also found that most drugs in the AD pipeline (76%) were disease-modifying therapies (DMTs), reflecting a strong emphasis on altering the disease course rather than merely managing symptoms. This focus underscores the priority placed on addressing the underlying pathology of AD to achieve long-term benefits for patients. The team examined the extent to which biomarkers were utilized in the clinical trials. They reported that in Phase 3 trials, amyloid PET was collected in 11 trials, cerebrospinal fluid (CSF) amyloid in 9 trials, and CSF amyloid/tau ratios in 2 trials. Additionally, tau PET was collected in 1 trial, CSF p-tau in 4 trials, and CSF tau in 2 trials. According to the authors, the integration of biomarkers has become increasingly prevalent in AD clinical trials, aiding in precise diagnosis and monitoring of therapeutic responses. This biomarker-driven approach enhances the ability to detect and quantify the impact of therapies on AD pathology, potentially improving trial outcomes and accelerating the development of effective treatments.

The researchers analyzed the proportion of new chemical entities (NCEs) and repurposed agents in the pipeline. They found that the 2024 pipeline included fewer NCEs (88) compared to 2023 (101), representing a 13% decrease. Repurposed agents remained relatively constant, with 39 in 2024 compared to 40 in 2023. The reduction in NCEs suggests a potential strategic shift towards optimizing and validating existing therapeutic approaches. Repurposed drugs, which constituted 31% of the pipeline, offer advantages such as known safety profiles and potentially expedited development timelines. This trend highlights an ongoing interest in leveraging existing drugs for new indications in AD. They also evaluated the duration of each trial phase and the time required for participant recruitment. They reported that on average, it takes 2.1 years to recruit participants for Phase 1 trials, 2.5 years for Phase 2 trials, and 3.2 years for Phase 3 trials and found  recruiting a sufficient number of participants for AD trials remains a significant challenge. The extended recruitment periods reflect the difficulties in enrolling individuals with AD, particularly for trials requiring specific behavioral or cognitive characteristics. Strategies to increase interest in trial participation and improve recruitment processes are essential for accelerating AD drug development.

Looking at the geographic distribution of the trials, the authors found that 56% of Phase 3 trials were conducted globally with both North American and non-North American sites, while 29% were performed in North America only, and 16% were conducted exclusively outside North America. The global distribution of trials highlights the international effort to combat AD. Conducting trials across diverse populations enhances the generalizability of findings and ensures that therapies are effective across different demographic and genetic backgrounds. International collaboration is crucial for advancing AD research and developing universally applicable treatments. In conclusion, the expert opinion and review of Professor Jeffrey Cummings and his team showcased detailed examination of the current AD drug development pipeline and provided critical insights into the state of therapeutic research, highlighting trends, gaps, and future directions. By comparing the 2024 pipeline to previous years, the study identifies trends and shifts in therapeutic targets and approaches. This information is invaluable for researchers and developers in adapting their strategies to align with the most promising areas of AD research. The study highlighted the priority placed on DMTs in the AD pipeline which emphasizes the industry’s commitment to addressing the underlying pathology of AD, rather than merely managing symptoms. Additionally, the analysis of biomarker integration in clinical trials demonstrates the reliance on biomarkers for diagnosis and therapeutic monitoring. This trend towards biomarker-driven approaches enhances the precision and effectiveness of AD research. It is noteworthy to mention, the study offers a clear picture of the therapeutic options currently under investigation for patients and clinicians and such valuable data and information can aid in making informed decisions about participating in clinical trials and exploring new treatment possibilities. According to the authors, despite the challenges in recruitment and the lengthy development timelines, the ongoing global efforts and collaborative research initiatives offer hope for the future of AD therapeutics.

Mapping the Current Landscape of Alzheimer's Disease Drug Development: Trends, Challenges, and Future Directions - Medicine Innovates

About the author

Dr. Jeffrey L. Cummings
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Research Professor, Department of Brain Health
Director, Chambers-Grundy Center for Transformative Neuroscience at UNLV

A world-renowned Alzheimer’s researcher and leader of clinical trials, Dr. Cummings has been recognized for his scientific and leadership contributions with the American Geriatrics Society’s Henderson Award (2006), the national Alzheimer’s Association’s Ronald and Nancy Reagan Research Award (2008), and the American Association of Geriatric Psychiatry’s Distinguished Scientist Award (2010).

Dr. Cummings’ interests embrace clinical trials, developing new therapies for brain diseases, and the interface of neuroscience and society. Dr. Cummings has published nearly 800 articles and 44 books devoted to neuroscience, Alzheimer’s disease, and clinical trials. Dr. Cummings received the Society for Behavioral and Cognitive Neurology’s Lifetime Achievement Award (2017), the International Society of CNS Drug Development’s Leadership and Achievement Award and the national Alzheimer’s Association’s Bengt Winblad Lifetime Achievement Award (2018).


Cummings J, Zhou Y, Lee G, Zhong K, Fonseca J, Cheng F. Alzheimer’s disease drug development pipeline: 2024. Alzheimer’s Dement. 2024; 10:e12465.

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