There is increasing focus on the development of new cell and gene therapies (CGT) in rare disease. The majority of CGT approvals have been based on small, open-label, non-randomized, single-arm studies which either evaluate treatment effectiveness without a comparator or utilize a historical control comparator to evaluate treatment efficacy. Among the several unique study design challenges common to CGT trials is the inability in many rare diseases to secure suitable historical controls that enrich the single-arm trial by providing an opportunity for evaluating efficacy.
In this presentation, we highlight key study design challenges and considerations for rare disease CGT trials and discuss the potential for leveraging in silico approaches for generating synthetic control arms that enable a control-based comparative assessment of efficacy.