Adeno-Associated Virus Gene Therapy Development: Early Planning and Regulatory Considerations to Advance the Platform...

Area of Science:

• Gene therapy development
• Rare disease therapeutics
• Adeno-associated virus (AAV) vectors

Background:

• Gene therapy development faces significant challenges, necessitating strategic early planning for successful implementation.
• The NIH's Platform Vector Gene Therapy (PaVe-GT) program focuses on developing AAV gene therapies for rare diseases using a platform approach.
• Establishing a Target Product Profile (TPP) is crucial for aligning preclinical studies with clinical objectives and guiding product development.

Purpose of the Study:

• To elaborate on the value of establishing a TPP and utilizing FDA INTERACT meetings in gene therapy development.
• To detail the experience of the PaVe-GT program in seeking early FDA feedback for their lead AAV gene therapy candidate, AAV9-hPCCA.
• To provide stakeholders with resources and lessons learned for navigating the regulatory path to clinical trial initiation.

Main Methods:

• Development of a Target Product Profile (TPP) for the AAV9-hPCCA investigational gene therapy.
• Engagement with the Food and Drug Administration (FDA) through an INitial Targeted Engagement for Regulatory Advice on CBER/CDER ProducTs (INTERACT) meeting.
• Documentation of the regulatory strategy, meeting experience, and lessons learned for public dissemination.

Main Results:

• The TPP and INTERACT meeting provided critical early feedback, establishing a regulatory strategy for the AAV9-hPCCA gene therapy.
• The PaVe-GT program successfully navigated preclinical development by aligning with regulatory requirements.
• Regulatory documents and templates are made available to aid other drug development programs.

Conclusions:

• Early establishment of a TPP and proactive engagement with the FDA via INTERACT meetings are vital for efficient gene therapy development.
• The PaVe-GT program's experience demonstrates a viable regulatory pathway for AAV gene therapies targeting rare diseases.
• Sharing regulatory learnings and resources can accelerate the initiation of first-in-human clinical trials for novel gene therapies.