Charting the Course: A Brief Recap of BGTC's Regulatory Playbook for AAV Gene Therapies

It’s an exciting time for the gene therapy industry, with 2024 predicted to be a “breakout year” and up to 17 potential FDA approvals.¹ As the industry is gaining momentum, much of the regulatory framework and industry guidelines are still being established, with leaders trying to collectively find the most efficient way to bring safe and efficacious gene therapies to market. 

Consequently, on February 6th, 2024, the Bespoke Gene Therapy Consortium (BGTC) published their first regulatory playbook to serve “…as a guiding framework for the development and regulatory submission of adeno-associated virus (AAV) gene therapies for rare diseases.”² The BGTC is the first initiative of the Accelerating Medicines Partnerships^® (AMP^®) program, a public-private partnership between the NIH, the U.S. Food and Drug Administration (FDA), multiple pharmaceutical and life sciences companies, nonprofits, and other organizations all working towards fostering the development of gene therapies for treating rare diseases. Other similar programs, such as the FDA’s Collaboration on Gene Therapies Global Pilot, seek aligned goals, namely global harmonization of regulatory standards for gene therapy.³‍

Taken together, there is an international effort to get safe and efficacious gene therapies to market quicker, and these consortiums help drive this goal forward. They also dovetail nicely with recent comments from Peter Marks, the FDA’s Director of the Center for Biologics Evaluation and Research, who has stated that the organization sees the accelerated approval pathway for rare disease gene therapies as integral to progress in the space.⁴‍

In the following blog, we pull out key points from the BGTC playbook to better understand its vision for gene therapy approval pathways. 

A Quick Overview of the BGTC Regulatory Playbook Version 1.0

The BGTC’s regulatory playbook is aimed at streamlining AAV-based gene therapy development and regulatory approval. The consortium is focused on achieving 4 interrelated goals:² 

1. Making AAV based therapeutics more accessible for a broad range of diseases, with optimized AAV vector production and improved therapeutic gene expression
2. Streamlining preclinical and product testing with standardized manufacturing requirements
3. Standardizing regulatory package submission
4. Designing a clinical development manual to share learnings that accelerate the approval of future gene therapies

The Importance of Platform-Based Technologies

Implementing platform-based technologies is one of the foundational pillars proposed by the BGTC to achieve its goals. While many definitions of a “platform technology” exist, the BGTC defines it as using previously generated data and information about specific components of approved or developed gene therapy products. 

In other words, a platform-based approach uses technologies and approaches that led to successful gene therapies use rather than “reinventing the wheel” to navigate the same preclinical, manufacturing, and regulatory challenges. Examples include the NIH-led PaVe-GT project, which is developing four gene therapies for distinct diseases using a single vector, manufacturing process, and team. 

FDA Meeting Preparedness 

The BGTC recommends close contact with the CBER and scheduling INTERACT and pre-IND meetings to guide AAV-based gene therapy development. In the INTERACT meeting, sponsors are allowed to get “...early advice from the FDA on chemistry, manufacturing, and controls (CMC), pharmacology/toxicology, and/or clinical aspects of their AAV gene therapy development program.”⁵ Due to concerns over AAV-based gene therapy safety profiles, complicated manufacturing, and new testing methodologies, the INTERACT meeting will assist sponsors in product characterization and pre-clinical studies and identify any issues with these studies or manufacturing processes. The pre-IND meeting is meant to provide regulatory feedback to a gene therapy sponsor before IND submission and first-in-human clinical studies. Due to the importance of this meeting, sponsors should have certain pre-clinical and CMC boxes checked, all of which are outlined in the BGTC playbook.

Here's How This Can Help Gene Therapy Developers in the Future

These are not all of the “take-homes” from the BCGT playbook, but they represent some of the key foundational advice that gene therapy developers should consider. At Form Bio, we have designed an AI platform, FORMsight^AI, which can provide scalable AAV vector design, manufacturing, and analytical predictions for millions of constructs in parallel. As your in silico partner for gene therapy development, we also make it easy to analyze immunotoxicity and other safety concerns, facilitating data preparation for INTERACT meetings, pre-IND meetings, and/or IND submissions.