The Coming of Age of Gene Therapy for the Treatment of Human Diseases: A Regulatory Perspective

Abstract

After many years of promising clinical results splashed with some serious adverse events, gene therapy has finally reached maturity, as demonstrated by the increasing number of medicinal products approved for commercialization by regulatory authorities. The approved products tackle monogenetic inherited diseases as well as cancer, include both in vivo and ex vivo approaches, and comprise mostly gene additions but also a genome-edited product, demonstrating proof of concept for most gene therapy modalities. Uncertainties still remain, especially on their long-term safety and efficacy, which can only be solved with time. These successes should not lead to self-complacency but rather stimulate the development of necessary improvements concerning manufacturing or the safety and efficacy profile. Here, we review the different categories of gene therapy medicinal products and highlight potential areas for improvement. Products approved for commercialization are taken as the basis for the discussion, since information on their assessment is publicly available. New products and manufacturing approaches under development are also reviewed, with an emphasis on the regulatory challenges expected for some of them.

Keywords: CAR-T cells; gene therapy medicinal products; genome editing; mRNA; manufacturing; recombinant AAV.