FDA Rare Disease Focus: New Cell and Gene Therapy Draft Guidances; Plausible Mechanism Pathway for Bespoke Therapies

This CLE webinar will provide an overview of FDA's recent efforts to promote greater transparency and efficiency in the development of cellular and gene therapy products (CGTs) and personalized, bespoke therapies for rare diseases. The panel will examine a trio of recently released FDA draft guidance documents highlighting expedited programs for regenerative medicine therapies, innovative designs for clinical trials of CGTs in small populations, and postapproval methods for capturing safety and efficacy data for CGTs. The panel will also discuss the new "plausible mechanism" pathway outlined in the New England Journal of Medicine (NEJM) and consider how it aligns with the principles reflected in the draft guidances. The panel will conclude with a discussion about continuing uncertainties created by recent FDA guidance and actions and potential impacts for developers of CGTs and other rare disease therapies.  

A trio of recently issued FDA draft guidances and an NEJM article co-authored by FDA Commissioner Martin Makary demonstrate the agency's focus on promoting greater transparency and increasing efficiency in the development of CGTs and bespoke, personalized therapies for the treatment of rare diseases.

FDA's Center for Biologics Evaluation and Research (CBER) issued the following new draft guidances in September 2025 to assist sponsors who are developing and conducting postapproval studies of CGTs that address the following:

1. Expedited Programs for Regenerative Medicine Therapies for Serious Conditions consolidates and updates expectations for sponsors of regenerative medicine therapies seeking to utilize the agency's Fast Track, Breakthrough Therapy, Priority Review, and Accelerated Approval programs by providing more detailed recommendations about the eligibility of regenerative medicine therapies for these programs and describing expanded flexibilities.

2. Innovative Designs for Clinical Trials of Cellular and Gene Therapy in Small Populations is high-level guidance that seeks to assist sponsors developing drugs and biologics for rare diseases to overcome the challenges that may arise due to limited data, small patient populations, or manufacturing complexities by providing a non-exhaustive list of innovative design options and considerations for patient selection.

3. Postapproval Methods to Capture Safety and Efficacy Data for Cell and Gene Therapy Products focuses on methods and data sources that can be used for tracking CGT postapproval safety and efficacy outcomes.

Additionally, in November 2025 FDA Commissioner Makary and CBER Director Vinay Prasad published an article in NEJM that proposed a new "plausible mechanism" pathway under which certain bespoke, personalized therapies may obtain FDA marketing authorization where a randomized trial is not feasible. However, significant questions remain including those as to FDA implementation.

Counsel should understand how the FDA's heightened focus on CGTs and personalized therapies will impact drug and biologic development and what compliance challenges may be faced by their clients.

Listen as our expert panel examines the FDA's new draft guidance documents related to CGTs and describes the "plausible mechanism" pathway as articulated by FDA leaders. The panel will discuss how the new "plausible mechanism" pathway aligns with the principles reflected in the draft guidances and offer best practices for compliance.