CHOP Expert Breaks Down Latest Hemophilia A Gene Therapy Data

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Lindsey A. George, MD Lindsey A. George, MD, Director of Clinical In Vivo Gene Therapy at Children's Hospital of Philadelphia (CHOP), recently provided an editorial in the New England Journal of Medicine in response to a phase 3 study of valoctocogene roxaparvovec, an AAV gene therapy for hemophilia A.

In the editorial, Dr. George, who leads the Novel Therapeutics for Bleeding Disorders (NoT Bleeding) Program in addition to the Clinical In Vivo Gene Therapy Group at CHOP, calls the study a major scientific accomplishment, as it is the largest AAV gene therapy trial to date. However, she points to questions raised by the study and cautions that future studies must answer and resolve these concerns for gene therapy to be a viable long-term therapeutic option for hemophilia A patients.

She points to both declining expression of factor VIII, the blood clotting factor that is deficient in hemophilia A patients, and variability of factor VIII expression across patients in the trial as limitations the field hopes to improve upon in subsequent iterations of hemophilia A gene therapy efforts. For gene therapies to achieve their purpose, patients must have sustained expression over time; if expression declines, patients will eventually need to revert to conventional treatments. Additionally, due to the nature of AAV gene therapy, once patients receive an AAV vector, infusion of another vector is unlikely to be successful, even if they lose expression entirely, as they will have developed antibodies to AAV.

“The goal of hemophilia gene therapy — to provide safe, durable, and predictable therapeutic benefit to all patients who receive a vector — has not wavered,” Dr. George writes. “Future efforts progressing to this ultimate objective will be informed by investigating and addressing questions that have emerged from this seminal accomplishment.”

Read more about her take on this phase 3 study here.

Contact: Jennifer Lee, The Children’s Hospital of Philadelphia, 267-426-6084 or

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