Mechanism of Action, Potency and Efficacy: Considerations for Cell and Gene Therapies

Published

April 1, 2024

Author(s)

Carl Simon Jr., Anne L. Plant, Catherine Zander, Erich Bozenhardt, Christina Celluzzi, David Dobnik, Melanie Grant, John Hughes, Uma Lakshmipathy, Kok-Seong Lim, Laura Montgomery, Hesham Nawar, Thiana Nebel, Linda Peltier, James Sherley, Rouzbeh Taghizadeh, Eddie Tan, Sandrine Vessillier

Abstract

One of the most challenging aspects of cell and gene therapy products (CGTPs) is defining mechanism of action (MOA), potency and efficacy of the product. This perspective examines these concepts and presents helpful ways to think about them through the lens of metrology. A logical framework for thinking about MOA, potency and efficacy is presented in a manner that is consistent with the existing regulatory guidelines but also accommodates what has been learned from the 32 US FDA approved CGTPs. Available information regarding MOA, potency and efficacy for the 32 US FDA-approved CGTPs is reviewed to provide background and perspective. A chart is provided that clarifies and distinguishes MOA, potency, potency test, efficacy, efficacy endpoint and efficacy endpoint tests, and illustrates the relationships between these concepts. Careful consideration of the meaning of these terms makes it easier to discuss the challenges of correlating potency test results with clinical outcomes and to understand how the relationships between the concepts may breakdown during development and clinical trials. Examples of how a product can be "potent but not efficacious" or "not potent but efficacious" are presented. An example application compares how MOA is assessed in cell cultures, animal models and human clinical trials and reveals the challenge of establishing MOA in humans. Lastly, important considerations for the development of potency tests for a CGTP are discussed. These ideas can help product developers to set appropriate expectations for understanding a product's MOA and potency, avoid unhelpful assumptions and improve communication among development team members during development of CGTPs.

Citation

Journal of Translational Medicine

Volume

22

Pub Type

Journals

Download Paper

https://doi.org/10.1186/s12967-024-05179-7

Local Download

Keywords

cell therapy, efficacy, potency, regenerative medicine, tissue engineered medical product

Citation

Simon Jr., C. , Plant, A. , Zander, C. , Bozenhardt, E. , Celluzzi, C. , Dobnik, D. , Grant, M. , Hughes, J. , Lakshmipathy, U. , Lim, K. , Montgomery, L. , Nawar, H. , Nebel, T. , Peltier, L. , Sherley, J. , Taghizadeh, R. , Tan, E. and Vessillier, S. (2024), Mechanism of Action, Potency and Efficacy: Considerations for Cell and Gene Therapies, Journal of Translational Medicine, [online], https://doi.org/10.1186/s12967-024-05179-7, https://tsapps.nist.gov/publication/get_pdf.cfm?pub_id=956604 (Accessed December 23, 2024)