title: 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.
authors.affiliation: Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, NV, USA. cumminj@ccf.org.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Cummings
authors.affiliation: University of Southern California, San Diego, CA, USA.
authors.forename: Paul S
authors.initials: PS
authors.lastname: Aisen
authors.affiliation: Institute for Memory and Alzheimer's Disease (IM2A) and ICM, Salpêtrière University Hospital, Paris University, Paris, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: DuBois
authors.affiliation: Department of Geriatric Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
authors.forename: Lutz
authors.initials: L
authors.lastname: Frölich
authors.affiliation: Department of Radiology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Clifford R
authors.initials: CR
authors.lastname: Jack
authors.affiliation: The Research Institute for the Care of Older People (RICE), Royal United Hospital, Bath, UK.
authors.forename: Roy W
authors.initials: RW
authors.lastname: Jones
authors.affiliation: Knight Alzheimer Disease Research Center, Washington University School of Medicine, St Louis, MO, USA.
authors.forename: John C
authors.initials: JC
authors.lastname: Morris
authors.affiliation: Eli Lilly and Company, Toronto, Canada.
authors.forename: Joel
authors.initials: J
authors.lastname: Raskin
authors.affiliation: Eli Lilly and Company, Indianapolis, IN, USA.
authors.forename: Sherie A
authors.initials: SA
authors.lastname: Dowsett
authors.affiliation: Department of Neurology & Alzheimer Center, VU University Medical Center, Amsterdam, Netherlands.
authors.forename: Philip
authors.initials: P
authors.lastname: Scheltens
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy*; D000818:Animals; D055808:Drug Discovery; D006801:Humans; D018697:Nootropic Agents / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D018697:Nootropic Agents
keywords: 2025; Alzheimer’s disease; Disease-modifying therapy