Safety, efficacy, and patient-reported outcomes 6 years after fidanacogene elaparvovec in adults with hemophilia B.

Fidanacogene elaparvovec is a single-dose gene therapy designed to express the high-activity factor IX (FIX) variant FIX-R338L. Participants (N = 15) with FIX activity of ≤2% were dosed with 5 × 1011 vector genomes per kilogram infusion of fidanacogene elaparvovec and completed the 1-year dosing trial. After the initial 52 weeks, participants could enroll in long-term follow-up (LTFU) for 5 additional years. This report includes final safety and efficacy data of the LTFU trial through 6 years after gene therapy, with additional patient-reported outcomes (PROs). Of 14 participants enrolled in the LTFU, 11 completed 6 years of follow-up. During years 2 to 6, 9 serious adverse events were reported in 4 participants (28.6%); none were considered treatment-related or resulted in study discontinuation or death. Eight participants had increased alanine aminotransferase levels, and 3 of 8 also had increased aspartate aminotransferase levels; none received corticosteroids. No liver masses, malignancies, thrombotic events, or FIX inhibitors were reported. FIX activity was maintained, with a mean FIX activity of 24.7% at year 2 (n = 14) and 26.1% at year 6 (n = 11). Mean treated annualized bleeding rates remained lower than 1.0 (median, 0.0) during each year of follow-up. Ten participants (71%) had no treated bleeding events. None of the 14 enrolled participants resumed FIX prophylaxis. Improvements relative to before gene therapy in PROs and target joints were observed over the duration of follow-up. Overall, fidanacogene elaparvovec exhibited a favorable safety profile, sustained efficacy, and improved PROs for up to 6 years. This trial is registered at www.clinicaltrials.gov as NCT03307980.