Clinical Development of Gene Therapies: The First Three Decades and Counting

Abstract

In the past three decades the field of gene therapy has made remarkable progress, surging from mere laboratory experiments to Food and Drug Administration (FDA)-approved products that bring significant reduction in disease burden to patients who previously had no therapeutic options for their serious conditions. Herein, we review the evolution of the gene therapy clinical research landscape and describe the gene therapy product development programs evaluated by the FDA in Investigational New Drug applications received in 1988-2019. We also discuss the clinical development programs of the first six oncolytic and gene therapy products approved in the United States.

Keywords: CBER; Center for Biologics Evaluation and Research; FDA; IND; Investigational New Drug application; OTAT; Office of Tissues and Advanced Therapies; gene therapy; natural history; product development; rare diseases.

Graphical abstract

Figure 1

IND Applications for Gene Therapy Product Programs Submitted in 1988–2019 The shaded area (all colors) corresponding to each year represents the total number of IND applications with gene therapy product development programs submitted that year.

Figure 2

Distribution of All Ongoing IND Applications by Therapeutic Area

Figure 3

Trends in IND Applications Sponsored by Academic and Commercial Entities

Figure 4

IND Applications by Product Categories Submitted in 1988-2019 GM cells, genetically modified cells without the use of genome-editing technologies; RV, retroviral vectors; AV, adenoviral vectors; AAV, adeno-associated viral vectors; PL, plasmids; MV, microbial vectors; GE, products with genome-editing technologies including both GM cells and in vivo genetic constructs.