Trial by “Firsts”: Clinical Trial Design and Regulatory Considerations in the Development and Approval of the First AAV Gene Therapy Product in the United States

Given the therapeutic potential of supplying a normal copy of a mutant gene to the correct target tissue, gene therapy holds extraordinary promise for the treatment of genetic disease. Like other novel classes of therapeutics however, gene therapies must overcome a range of clinical, regulatory, and manufacturing hurdles to reach regulatory approval. This paper reviews key aspects of clinical trial design, development, and evaluation of a novel primary end point, and regulatory interactions that resulted in the first approval by the U.S. Food and Drug Administration (FDA) of an adeno-associated virus (AAV) gene therapy product.