Patient Education on AAV Vectors for Hemophilia Essential to Prevent ‘Buyer’s Remorse’

Having long served as the model disorders for the development of gene therapy, hemophilia A (HA) and hemophilia B (HB) are currently benefitting from the role with the emergence of adeno-associated viral (AAV) vectors, according to a review article published in the Annual Review of Medicine.

“HA and HB AAV vectors in clinical development are distinguished by outcomes, including level of transgene-derived factor activity, durability of expression, heterogeneity between n recipients, and annualized bleeding rate,” wrote Benjamin J Samelson-Jones, MD, PhD, and Lindsey A George, MD, both of the University of Pennsylvania Perelman School of Medicine and the Children’s Hospital of Philadelphia.

The article provides an overview of AAV gene therapy development for patients with HA and HB. Because successful strategies targeting AAV-neutralizing antibodies to allow for vector readministration remain elusive, true informed patient consent for treatment requires a solid understanding of the AAV platform and the individual vector, the authors advised.

“Patients should be counseled so that they are fully aware that the current state of clinical development likely only permits one lifetime systemic AAV vector administration; this is important to prevent ‘buyer’s remorse’ should one vector ultimately be inferior to another,” they wrote, “and underscores the importance of comprehensive understanding of all available information of each vector prior to administration to ensure a well-informed decision.”

Despite proof-of-concept successes in HA and HB gene therapy, durable factor expression able to ameliorate bleeding in all patients is an unrealized hope at this point, according to the review.

“This,” the authors wrote, “defines the development goals of the next generation of gene-based therapies for hemophilia.”

Reference

Samelson-Jones BJ, George LA. Adeno-associated virus gene therapy for hemophilia. Annu Rev Med. 2023;74:231-247. doi:10.1146/annurev-med-043021-033013