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 ≤2% were dosed with 5×1011 vector genomes/kg 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 reports includes final safety and efficacy data of the LTFU trial through 6 years post gene therapy, with additional patient-reported outcomes (PROs). Of 14 participants enrolled in the LTFU, 11 completed 6-years' follow-up. During Years 2 to 6, 9 serious adverse events (AEs) 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 pre-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.
Samelson-Jones et al. (Tue,) studied this question.