Keywords: cell or gene-editing treatment, single-arm studies, small cohort of patients, historical studies, natural history studies
Room: Madison A
There are up to 7000 different rare diseases in the world, many of which are serious and life-threatening genetic diseases. With the advancement of cell therapies and gene-editing technology, more and more investigational products based on these technologies are being brought under clinical development with the objective of bringing transformative medicines to patients carrying certain underlying genetic mutations. Due to ethical and practical reasons, clinical developments of cell or gene-editing treatments are often carried out through single-arm studies in a relatively small cohort of patients. Understanding disease progression, evaluating biomarkers / surrogate endpoints, the ability of predicting the effectiveness based on surrogate biomarkers, and evaluating safety endpoints uniquely related to cell or gene therapies, rely heavily on data from historical randomized clinical trials and/or natural history studies. In some situations, data from natural history studies can also be used to choose primary or key secondary efficacy endpoints for the pivotal studies. At the round table discussion, we will review different types of historical data and the use of historical study data in designing and monitoring the pivotal studies for cell or gene therapies. We will also discuss the limitations of using different types of historical data as external control.