Choice of Disease Target Could Shorten Clinical Trials for Gene Therapies

February 17, 2023

More progressive diseases with rapid onset may involve shorter trials

The Office of Tissues and Advanced Therapies (OTAT), part of the Food and Drug Administration's Center for Biologics Evaluation and Research (CBER), has begun a series of virtual town halls to answer questions about a variety of areas where OTAT has regulatory oversight. On Feb. 7, OTAT hosted one such town hall on the clinical development of gene therapy products for rare diseases, excluding hematology/oncology products.

During this town hall, OTAT officials said that the duration of clinical trials for gene therapies depends on the nature of the disease being treated and that more progressive diseases with rapid onset may involve shorter trials. Officials also said there is no one-size-fits-all approach to determining the necessary duration of clinical trials; instead, the duration varies based on the type of disease the therapy is intended to treat.

Other areas of discussion open for questions included:

  • Factors sponsors should consider when determining the study population for early phase gene therapy trials
  • OTAT's criteria for allowing single-arm, externally controlled trials to provide the primary evidence of effectiveness for approval

When considering the factors around study population, OTAT officials said sponsors should conduct a benefit-risk analysis to ensure that patients who would benefit the most from the therapy are given enrollment preference and to ensure they are otherwise healthy because of toxicity risk. The officials also noted their preference for enrolling those who can provide informed consent (i.e., adult versus pediatric), at least for the collection of preliminary safety data.

Asked to specify whether the agency will allow the use of single-arm, externally controlled studies in lieu of two well-controlled randomized studies to evaluate the efficacy of new gene therapies, officials said that regulatory approval for gene therapies hinges on substantial evidence of efficacy from an adequate and well-controlled study. The officials also said the agency will permit external controls, such as natural history controls or concurrent controls for gene therapy trials to treat rare and serious diseases under certain conditions. These would include cases involving diseases with well-understood underlying pathogeneses and a well-documented and highly predictable course that can be objectively measured and verified.

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