Monthly Roundup: June 2024
Presented by: Pratima Chowdary, MD, MRCP, FRCPath
The GO-8 study is evaluating a novel AAV-based gene therapy for severe hemophilia A. This phase 1/2 trial assessed safety and efficacy across four dose levels, using a serotype-8 capsid and a truncated B-domain Factor VIII transgene, enabling threefold higher expression than standard designs. Among 12 participants, the 2x10¹² vg/kg dose cohort showed the most stable Factor VIII expression over four years, with levels stabilizing by 52 weeks and remaining consistent.
Higher doses achieved higher initial Factor VIII levels but were less stable, with some participants experiencing immune-mediated loss of expression. Notably, 75% of participants discontinued prophylaxis. Prophylactic and reactive immunosuppression managed immune responses effectively. Recruitment in the optimal dose cohort will continue to confirm durability and consistency.
