Both the FDA and the EMA have independently reached favorable decisions on the value of independent nonprofit Critical Path Institute’s (C-Path) new disease simulation tool for improving trial design in mild and moderate Alzheimer’s disease (AD).

The first such instrument to receive this regulatory designation, 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. The goal is to serve as a public resource for sponsors designing trials of new therapies.

On June 12, the FDA issued a regulatory letter to C-Path’s consortium, the Coalition Against Major Diseases (CAMD), an organization of over 150 scientists from pharmaceutical companies, CROs, regulatory agencies, patient advocacy organizations, academic institutions and government agencies. The letter stated the tool was a “fit-for-purpose” drug development tool.

“Model-based drug development was one of the goals defined in FDA’s 2004 Critical Path Initiative report, and this new tool sets the stage for applying new technologies to accelerating medical product development,” said Janet Woodcock, M.D., director of the Center for Drug Evaluation and Research (CDER) at the FDA.

“The proposed Disease Progression and Trial Evaluation Model is suitable for use in drug development as a longitudinal model for describing changes in cognition in patients with mild and moderate AD, and for use in trial designs in mild and moderate AD,” said the EMA's Committee on Human Medicinal Products (CHMP) on June 27. The CHMP is the EMA committee responsible for preparing opinions on questions concerning medicines for human use.

This new 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 succeed.

“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,” said Richard Lalonde, PharmD, vice president and global head of clinical pharmacology at Pfizer. “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.”

“Alzheimer’s disease clinical development tools, derived from real-world findings, take into account a variety of factors to increase our confidence that a clinical study is accurately designed to detect a treatment effect,” said Richard Mohs, Ph.D., vice president, early-phase neuroscience clinical research at Eli Lilly and a member of the CAMD coordinating committee. “This model provides valuable insight into the relatively slow rate of disease progression in a mild patient population—a critical area of focus for drug development—and guidance for designing an effective study in multiple populations, while emphasizing the need to refine the model as we work to treat patients earlier in the disease process and as new data emerges."

"The regulatory decisions on this tool exemplify how C-Path's efforts result in alignment between global regulatory agencies when based on consensus science and supporting data; an alignment that can result in greater efficiency in drug development,” said Martha Brumfield, Ph.D., president and chief executive officer of C-Path. “This could not have been accomplished by any one entity working in isolation.”