AAV Gene Transfer Feasible for the Treatment of Hemophilia A

In a phase 1-2 trial, 16 of 18 men had sustained expression of factor VIII after gene transfer with adeno-associated viral vector (SPK-8011)

TUESDAY, Nov. 30, 2021 (HealthDay News) -- Patients with hemophilia A who receive an investigational adeno-associated viral (AAV) vector (SPK-8011) for hepatocyte expression of factor VIII exhibit sustained factor VIII expression, as well as a reduction in bleeding episodes, according to a study published in the Nov. 18 issue of the New England Journal of Medicine.

Lindsey A. George, M.D., from the University of Pennsylvania in Philadelphia, and colleagues infused SPK-8011 in 18 men with hemophilia A in a phase 1-2 trial that included four dose cohorts.

The researchers found that during a median safety observation period of 36.6 months, 33 treatment-related adverse events occurred in eight participants; 17 were vector-related, including one serious adverse event, and 16 were related to the glucocorticoid. Due to an anti-AAV capsid cellular immune response that was not sensitive to immune suppression, two participants lost all factor VIII expression. Factor VIII expression was maintained in the remaining 16 participants; 12 were followed for more than two years and there was no apparent decrease in activity over time. The annualized bleeding rate decreased by 91.5 percent (median rate, 8.5 and 0.3 events per year before versus after vector administration).

"These data support our hypothesis that liver-directed AAV gene therapy is a viable approach for long-term treatment of hemophilia A," George said in a statement. "Future research will aim to further improve on this work to safely achieve sustained, stable, and predictable FVIII levels in all hemophilia A patients."

Several authors disclosed financial ties to the biopharmaceutical industry, including Spark Therapeutics, which partially funded the study.

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