To evaluate Annualized Bleeding Rate (ABR), Factor (F)VIII consumption, corticosteroid use, quality of life (QoL) and safety outcomes after 4-years post-gene transfer in the Brazilian cohort.

In the GENEr8-1 trial (NCT03370913), a cohort of 18 Brazilian men with severe hemophilia A (FVIII ≤1 IU/dL) without inhibitors were infused with 6×10̂13 vg/kg valoctocogene roxaparvovec. Self-reported ABR and FVIII consumption (after Week [W] 4) through data cutoff were compared to baseline. QoL per Haemo-QOL-A and EQ-5D-5L, corticosteroid utilization and safety were assessed.

Eighteen participants (mean [Standard Deviation, SD] age, 28.3 [6.8]; mean [SD] weight, 81.2 kg [19.4]) completed 4-years of follow-up. Six (33.3%) participants presented with any grade 3 and above adverse events (AE). No participants initiated corticosteroids after W13. At year (Y) 4, 9 participants (50%) hadn't presented any treated bleeds and treated ABR was 0.4 (SD 0.8). Annualized FVIII utilization was 63.91 U/kg/yr (SD 114.61) W5 up to W208. As for QoL, mean±SD for HEMO-QoL-A was 7.8±10.7 and for EQ-5D was 0.04±0.12 at Y4, with an improvement from baseline exceeding the anchor-based clinically important difference (5.5 and 0.03, respectively).

The safety profile of valoctocogene roxaparvovec in the Brazilian cohort is consistent with previously observed in the GENEr8-1 ITT population, with no new safety signals. In Y4, ABR maintained a reduction of over 70% from the baseline and clinically relevant improvements in Haemo-QOL-A Total Score and EQ-5D-5L were also observed.

After 4-years of follow-up, a single infusion of valoctocogene roxaparvovec provided durable bleeding protection and improved QoL with acceptable safety profile in Brazilian patients. The robust hemostatic efficacy relative to FVIII prophylaxis and the safety profile promoted by valoctocogene roxaparvovec in the Brazilian cohort were not distinct from the previously observed in the whole study cohort.