Drug development in Alzheimer’s disease: the path to 2025

Abstract

The global impact of Alzheimer’s disease (AD) continues to increase, and focused efforts are needed to address this immense public health challenge. National leaders have set a goal to prevent or effectively treat AD by 2025. In this paper, we discuss the path to 2025, and what is feasible in this time frame given the realities and challenges of AD drug development, with a focus on disease-modifying therapies (DMTs). Under the current conditions, only drugs currently in late Phase 1 or later will have a chance of being approved by 2025. If pipeline attrition rates remain high, only a few compounds at best will meet this time frame. There is an opportunity to reduce the time and risk of AD drug development through an improvement in trial design; better trial infrastructure; disease registries of well-characterized participant cohorts to help with more rapid enrollment of appropriate study populations; validated biomarkers to better detect disease, determine risk and monitor disease progression as well as predict disease response; more sensitive clinical assessment tools; and faster regulatory review. To implement change requires efforts to build awareness, educate and foster engagement; increase funding for both basic and clinical research; reduce fragmented environments and systems; increase learning from successes and failures; promote data standardization and increase wider data sharing; understand AD at the basic biology level; and rapidly translate new knowledge into clinical development. Improved mechanistic understanding of disease onset and progression is central to more efficient AD drug development and will lead to improved therapeutic approaches and targets. The opportunity for more than a few new therapies by 2025 is small. Accelerating research and clinical development efforts and bringing DMTs to market sooner would have a significant impact on the future societal burden of AD. As these steps are put in place and plans come to fruition, e.g., approval of a DMT, it can be predicted that momentum will build, the process will be self-sustaining, and the path to 2025, and beyond, becomes clearer.

A roadmap to advance dementia research in prevention, diagnosis, intervention, and care by 2025

“…A core theme throughout the road map development was to address inequalities in access and outcomes between people affected by dementia. It was agreed that the purpose of the road map was not to set a pathway to discovering new pharmacological treatments and diagnostics, which has been covered elsewhere 8. However, the road map includes recommendations for biomedical and pharmaceutical research where relevant to improving real‐world outcomes.…”

“…There have been several dementia research road maps developed to date, but their implementation remains a challenge 5, 6, 7, 8. Effective implementation of this road map will require funding, a high level of coordination between different stakeholders, and maintained high‐level national priority to be given to dementia.…”

The emerging roles of protein homeostasis‐governing pathways in Alzheimer's disease

“…At present, no medication is available to delay or halt disease progression. Instead, cholinesterase inhibitors (donepezil, galantamine, rivastigmine, and tacrine), NMDA (N‐methyl‐D‐aspartate) receptor antagonists (memantine), and some neural protective agents are utilized in a sole or synergistic manner to ameliorate the symptoms caused by neuronal loss, especially cognitive defects (Cummings, Aisen, DuBois, Frölich, & Jack, 2016). Therefore, a thorough understanding of the pathogenesis of AD is necessary in order for more effective and targeted therapeutics to be developed.…”

Alzheimer’s Disease: New Diagnostic Criteria and Therapeutic Aspects Depending on the Stage of the Disease

“…Распростра ненность этого заболевания неуклонно увеличивается с возрастом, и, согласно мировым тенденциям, в ближайшие 30 лет можно ожидать увеличения числа больных БА в 3-4 раза до 131,5 млн человек в 2050 г. [13]. Это позволяет считать БА пандемией XXI в.…”