Gene Therapies - When Does Research End and Treatment Begin?

Abstract: The first gene replacement therapy for an inherited genetic disease was approved in the USA in 2017. In early 2025, there were thirteen approved products, with dozens more in active clinical trials. Gene replacement and gene editing products are quite different from typical drugs and biologics, most notably because they can only be given once, and cannot be turned up, turned down, reversed or otherwise modified, once administered. Additionally, these products must be monitored, often for a decade or more to ensure reporting of the durability of efficacy as well as to characterize any late to emerge risks, such as malignancies. Such long tails on safety and efficacy monitoring put trial participants and some early adopters for treatment with newly approved gene therapies into a unique category of both research participant, and as a recipient, treated with an ostensibly proven to be safe and effective product. Such blurring of the research versus treatment lines does not exist, or exists much less frequently in the continuum of research and approval of small molecule drugs and biologics, especially those not being developed for rare conditions. This presentation will discuss the implications of this gray zone on how we define research versus treatment, as well as on elements of consent, volunteerism, data collection and reporting, and the implications of abandoning gene therapy programs when years to a decade or more of additional safety monitoring is required.

Keywords: gene therapy and gene editing, research ethics, duty to report research results