FDA Offers Refined Gene Therapy Clinical Trial Expectations

FDA Commissioner Scott Gottlieb, MD

FDA Commissioner Scott Gottlieb, MD

A new series of guidances from the U.S. Food and Drug Administration (FDA) proffer a number of goals, including articulation of the agency’s expectations regarding how sponsors should provide sufficient chemistry, manufacturing, and control (CMC) information to address safety issues in the nascent world of human gene therapy.

Commissioner Scott Gottlieb said the agency plans to make full use of its expedited programs, such as the breakthrough therapy designation and regenerative medicine advanced therapy designation, whenever possible. The guidances are widely viewed as one way to encourage thoughtful gene therapy-related clinical research. In his tenure as FDA commissioner, Gottlieb has demonstrated a proactive approach some critics did not anticipate when was awarded the post.

Among other details, the draft guidances offer recommendations for clinical trial designs for gene therapies for hemophilia, including surrogate endpoints for sponsors hoping for accelerated approval for such therapies. Sponsors seeking a traditional approval pathway are advised to use the annualized bleeding rate as the primary endpoint to demonstrate clinical benefit. Sponsors who want accelerated approval may use factor activity as a surrogate endpoint for primary efficacy assessment.


Free for ACRP Members: An Introduction to Gene Therapy Research – This webinar replay summarizes the current state of gene therapy research and the associated risks. Learn how to obtain the necessary regulatory approvals and prepare sites to conduct gene therapy research. View Program Details

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In a separate draft guidance on rare diseases, the agency notes that while the demonstration of clinical benefit generally follows the same principles as for other products, the unique characteristics of a gene therapy often call for a broader perspective in selecting endpoints for rare diseases (e.g., some diseases are too rare to have well-established, disease-specific efficacy endpoints).

Another separate, but related, draft guidance on gene therapies for retinal disorders provides several established efficacy endpoints, including best corrected distance visual acuity and rate of photoreceptor loss.

Author: Michael Causey