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

Richa Madan Lomash; Jean Dehdashti; Oleg A Shchelochkov; Randy J Chandler; Lina Li; Irini Manoli; Jennifer L Sloan; Pramod Terse; Xin Xu; Dimah Saade; Rodica Stan; Philip J Brooks; Donald C Lo; Carsten G Bönnemann; Charles P Venditti; Anne R Pariser; Elizabeth A Ottinger; PaVe-GT team

doi:10.1089/hum.2024.230

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

Journal article

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

Richa Madan Lomash, Jean Dehdashti, Oleg A Shchelochkov, Randy J Chandler, Lina Li, Irini Manoli, Jennifer L Sloan, Pramod Terse, Xin Xu, Dimah Saade, …

Human gene therapy, Vol.36(5-6), pp.653-662

03/01/2025

DOI: 10.1089/hum.2024.230

PMCID: PMC11971537

PMID: 39976996

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Abstract

Gene therapy development presents multiple challenges, and early planning is vital in the successful implementation of such programs. The Platform Vector Gene Therapy (PaVe-GT) program is a National Institutes of Health (NIH) initiative developing adeno-associated virus (AAV) gene therapies for four low-prevalence rare diseases. Utilizing the platform-based approach, the program aims to incorporate efficiencies throughout the preclinical and clinical development processes followed by public dissemination of scientific and regulatory learnings. Early in development, the establishment of a Target Product Profile (TPP) by the research team is a critical step to guide product development and align preclinical studies to clinical objectives. Based on the specific needs of the investigational product as defined in the TPP, an overall regulatory strategy can then be outlined to meet the regulatory requirements for the first-in-human clinical trials. During the preclinical phase of development, sponsors may request meetings with the Food and Drug Administration (FDA) to gather feedback on the planned studies and regulatory strategy. To pave the way for PaVe-GT's first investigational AAV gene therapy lead candidate, AAV9-hPCCA, we sought early feedback from the FDA utilizing an INitial Targeted Engagement for Regulatory Advice on CBER/CDER ProducTs (INTERACT) meeting. Here, we elaborate on the value of establishing a TPP and the FDA INTERACT meeting by including our initial AAV9-hPCCA TPP, detailing our INTERACT meeting experience, providing all corresponding regulatory documentation, and highlighting lessons learned. The regulatory documents along with templates developed by our program can also be found on the PaVe-GT website (https://pave-gt.ncats.nih.gov/). This communication aims to provide stakeholders with resources that can be applied to drug development programs in establishing a viable regulatory path to clinical trial initiation.

Gene Therapy

rare diseases

target product profile

propionic acidemia

PCCA

PaVe-GT

INTERACT meeting

AAV9

Details

Title: Subtitle: Adeno-Associated Virus Gene Therapy Development: Early Planning and Regulatory Considerations to Advance the Platform Vector Gene Therapy Program
Creators: Richa Madan Lomash - National Center for Advancing Translational Sciences
Jean Dehdashti - National Center for Advancing Translational Sciences
Oleg A Shchelochkov - National Human Genome Research Institute
Randy J Chandler - National Human Genome Research Institute
Lina Li - National Human Genome Research Institute
Irini Manoli - National Human Genome Research Institute
Jennifer L Sloan - National Human Genome Research Institute
Pramod Terse - National Center for Advancing Translational Sciences
Xin Xu - National Center for Advancing Translational Sciences
Dimah Saade - National Institute of Neurological Disorders and Stroke
Rodica Stan - National Center for Advancing Translational Sciences
Philip J Brooks - National Center for Advancing Translational Sciences
Donald C Lo - National Center for Advancing Translational Sciences
Carsten G Bönnemann - National Institute of Neurological Disorders and Stroke
Charles P Venditti - National Human Genome Research Institute
Anne R Pariser - National Center for Advancing Translational Sciences
Elizabeth A Ottinger - National Center for Advancing Translational Sciences
PaVe-GT team
Resource Type: Journal article
Publication Details: Human gene therapy, Vol.36(5-6), pp.653-662
DOI: 10.1089/hum.2024.230
PMID: 39976996
PMCID: PMC11971537
NLM abbreviation: Hum Gene Ther
ISSN: 1043-0342
eISSN: 1557-7422
Publisher: MARY ANN LIEBERT, INC
Grant note: NCATS Cures Acceleration NetworkNCATS Intramural Research Program: 1ZIATR00281 NHGRI: 1ZIAHG200318 NINDS: 1ZIANS003129-14
PaVe-GT is funded by the NCATS Cures Acceleration Network. R.M.L., P.T., X.X., R.S., D.C.L. and E.A.O. are supported by NCATS Intramural Research Program (1ZIATR00281). R.J.C., O.S., L.L., J.L.S., I.M. and C.P.V. are supported by Intramural Research Program of the NHGRI (1ZIAHG200318). D.S. and C.G.B. are supported by the NINDS Intramural Research Program (1ZIANS003129-14).
Language: English
Electronic publication date: 02/20/2025
Date published: 03/01/2025
Academic Unit: Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Neurology (Pediatrics)
Record Identifier: 9984793878302771

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