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A landmark for AD
TUCSON, Ariz.—In what may be a big step forward for Alzheimer's disease (AD) therapy development, both the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have independently reached favorable decisions on the value of the Critical Path Institute's (C- Path) new disease simulation tool for improving trial design in mild and moderate AD.
The first such instrument to ever receive this regulatory designation—deemed "fit for purpose" by the FDA and "suitable for use" by the EMA—the tool represents an enabling advance to improve the design of future clinical trials in AD. The new tool applies computerized models to simulate "what-if" scenarios for clinical trials, with the goal of serving as a public resource for sponsors designing trials of new therapies.
The FDA issued its "fit for purpose" regulatory letter to the Critical Path Institute's consortium, the Coalition Against Major Diseases (CAMD), in June.
"Model-based drug development was one of the goals defined in the FDA's 2004 Critical Path Initiative report, and this new tool sets the stage for applying new technologies to accelerating medical product development," says Dr. Janet Woodcock, director of the Center for Drug Evaluation and Research (CDER) at the FDA.
"The involvement of the FDA and the EMA for guidance on C-Path programs is a hallmark of C- Path/CAMD," says Dr. Diane Stephenson, executive director of the CAMD. She points out that C-Path programs frequently result in a formal regulatory qualification by FDA and EMA as drug development tools and novel methodologies. The institute is an independent, nonprofit organization established in 2005 with public and private philanthropic support from the Arizona community, the Science Foundation Arizona (SFAz) and the FDA. An international leader in forming collaborations to advance its mission of improving health and saving lives by accelerating the development of safe, effective medicines, C-Path has established global, public-private partnerships that currently include more than 1,000 scientists from government regulatory agencies, academia, patient advocacy organizations and 35 major pharmaceutical companies.
"The AD clinical trial simulation tool will make it possible to simulate clinical trials by integrating all relevant data so future studies will be more efficient and more likely to be successful," states Stephenson. "The tool was developed by integrating diverse sources of data which helped with improved reliability and confidence in the model."
The data sources used to develop the simulation include: Mild and moderate AD trials from the CAMD database—3,200 patient-strong at the time the tool was developed; 6,500 to date.
"Pfizer, Abbott (now AbbVie), AstraZeneca, Sanofi and GlaxoSmithKline all contributed data to the CAMD database," Stephenson notes. "There were nine trials in total, representing the placebo arms of legacy clinical trials."
Other sources included natural history data from the large observational study, the Alzheimer's Disease Neuroimaging Initiative (ADNI) mild and moderate AD cohort, which was 284 patient-strong at the time the tool was developed, and literature data from 73 publications of unique trials that represented more than 72,000 patients.
In earlier work, Stephenson notes, C-Path identified the first preclinical safety biomarkers, qualified by the FDA, the EMA and the PMDA, that predict whether a drug may affect kidney function and the first imaging biomarker for trial enrichment qualified by EMA in which clinicians can identify those patients with memory loss that are most likely to progress to Alzheimer's disease by measuring hippocampal volume.
Dr. Richard Lalonde, vice president and global head of clinical pharmacology at Pfizer, states, "this model was made possible because major pharmaceutical companies participating in CAMD were willing to share de- identified patient-level data for over 6,000 patients who previously participated in AD trials. The data from these trials were the basis for this model, and the FDA's decision on this tool will allow sponsors to apply modeling and simulation and launch AD trials with a higher degree of confidence. This is a great example of a rising tide lifting all boats."