Addressing Efficacy Uncertainties in Expedited Programs for Gene Therapy Products: A Comparative Assessment of Post-Approval Requirements by the FDA and EMA.
6 affiliations
- 1Department of Clinical and Translational Research Methodology, Institute of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8575, Ibaraki, Japan.
- 2Doctoral Program in Medical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8575, Ibaraki, Japan.
- 3Tsukuba Clinical Research & Development Organization, University of Tsukuba, 2-1-1 Amakubo, Tsukuba 305-8576, Ibaraki, Japan.
- 4Department of Neurosurgery, Mito Kyodo General Hospital, Tsukuba University Hospital Mito Area Medical Education Center, 3-2-7 Miyamachi, Mito 310-0015, Ibaraki, Japan.
- 5Department of Neurosurgery, Institute of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8575, Ibaraki, Japan.
- 6Center for Cybernics Research, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8575, Ibaraki, Japan.
Abstract
Expedited programs accelerate the availability of gene therapy products but frequently leave uncertainties regarding efficacy at approval. How post-approval requirements are utilized to complement these specific evidence gaps remains unclear. To address this, we conducted a detailed analysis of 18 gene therapy products granted Accelerated Approval (AA) by the FDA or conditional marketing authorization (CMA) by the EMA between January 2015 and September 2025. By reviewing official regulatory documents, we examined the efficacy-related uncertainties at the time of approval and the corresponding post-approval requirements. For AA, six of eight products (75.0%) were based on surrogate biomarkers or tumor response-based endpoints, with postmarketing requirements aimed at confirmatory evidence to verify clinical benefit. In contrast, seven of eleven CMA products (63.6%) were supported by disease-specific clinical outcomes, with specific obligations requiring final study results, extended follow-up, additional clinical studies, or registry-based data collection to complete the evidence package. Descriptive differences in post-approval evidence requirements were observed among the FDA AA and EMA CMA products included in this study, although the sample was limited. Early engagement with regulatory authorities may support flexible development strategies aligned with evolving regulatory expectations. It may also support post-approval evidence planning to address residual uncertainty.
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BibTeX
@article{nakamura2026addressing,
title = {{Addressing Efficacy Uncertainties in Expedited Programs for Gene Therapy Products: A Comparative Assessment of Post-Approval Requirements by the FDA and EMA.}},
author = {Kimika Nakamura and Yasuyuki Takashima and Shinya Watanabe and Aiki Marushima and Koichi Hashimoto},
journal = {Biotech (Basel (Switzerland))},
year = {2026},
month = sep,
doi = {10.3390/biotech15040082},
url = {https://europepmc.org/article/MED/42930060},
note = {CC BY},
}
RIS
TY - JOUR
TI - Addressing Efficacy Uncertainties in Expedited Programs for Gene Therapy Products: A Comparative Assessment of Post-Approval Requirements by the FDA and EMA.
AU - Kimika Nakamura
AU - Yasuyuki Takashima
AU - Shinya Watanabe
AU - Aiki Marushima
AU - Koichi Hashimoto
PY - 2026
DA - 2026/09/25
JO - Biotech (Basel (Switzerland))
DO - 10.3390/biotech15040082
UR - https://europepmc.org/article/MED/42930060
AB - Expedited programs accelerate the availability of gene therapy products but frequently leave uncertainties regarding efficacy at approval. How post-approval requirements are utilized to complement these specific evidence gaps remains unclear. To address this, we conducted a detailed analysis of 18 gene therapy products granted Accelerated Approval (AA) by the FDA or conditional marketing authorization (CMA) by the EMA between January 2015 and September 2025. By reviewing official regulatory documents, we examined the efficacy-related uncertainties at the time of approval and the corresponding post-approval requirements. For AA, six of eight products (75.0%) were based on surrogate biomarkers or tumor response-based endpoints, with postmarketing requirements aimed at confirmatory evidence to verify clinical benefit. In contrast, seven of eleven CMA products (63.6%) were supported by disease-specific clinical outcomes, with specific obligations requiring final study results, extended follow-up, additional clinical studies, or registry-based data collection to complete the evidence package. Descriptive differences in post-approval evidence requirements were observed among the FDA AA and EMA CMA products included in this study, although the sample was limited. Early engagement with regulatory authorities may support flexible development strategies aligned with evolving regulatory expectations. It may also support post-approval evidence planning to address residual uncertainty.
SN - 2673-6284
ER -