Abstract: In calendar 2023, five new gene therapies were approved in the United States, bringing the total number of approvals in that class to ten. Many of these programs employ dose-escalation designs during early clinical development to translate effective preclinical doses into safe and efficacious doses in humans. Unlike drugs and biologics, however, gene therapies cannot be turned up, down, or off, and cannot currently be re-dosed. The permanence of limited, or lack of efficacy, and limitations for future research opportunities for early research participants is significant, and these distinguish early gene therapy from traditional drug and biologics development. One of the exchanges for the possibility that a research participant may not directly benefit is the prospect of providing generalizable knowledge of potential use to future participants in research, or others with that condition. As appropriate doses are sought, many gene therapies continue to create groups of research participants who were under-dosed, or dosed outside an optimal time/age window to halt accumulating disability. Prior gene therapy recipients are often also excluded from other clinical trials for myriad reasons, limiting future prospects of direct benefit. The burden this population bears, as contributors of generalizable knowledge versus prospective beneficiaries is significantly different than research participants in traditional drug trials. It is reasonable to ask whether the scientific community is pursuing strategies to limit these numbers, whether we are appropriately honoring such accrued altruism, and whether opportunities to address this problem are feasible. Ideas to address this unique problem will also be presented.
Learning Objectives:
After participating in this conference, attendees should be able to:
Understand the differces and ethical concerns between traditional early drug development and early development of gene therapies.
Illustrate the existence of a unique group of early research participants that may bear a disproportionate burden versus those who participate in early traditional drug trials.
Propose methods and ideas to limit, honor and hopefully ameliorate such disproportionate burdens borne by early gene therapy research participants