PB0213 - Results from B-LIEVE, a Phase 1/2 Dose-Confirmation Study of FLT180a AAV Gene Therapy in Patients with Hemophilia B

Background: FLT180a (verbrinacogene setparvovec) is an investigational gene therapy for the treatment of hemophilia B that uses a rationally designed AAVS3 capsid carrying a gain-of-function factor IX (FIX) Padua (R338L) transgene. B-AMAZE was a Phase 1/2 dose-finding study of FLT180a in 10 patients with hemophilia B (FIX ≤2%) who also received prophylactic immune management with corticosteroids ± tacrolimus. FIX expression was dose dependent, and FIX levels in the normal range (50-150%) were observed in 5 of 10 patients at most recent follow-up. B-LIEVE is a Phase 1/2 study of FLT180a manufactured with a commercial process that began enrollment in early 2022 and is intended to confirm the dose and immune management regimen for Phase 3.

Aims: Present safety and FIX activity data for patients treated with FLT180a in B-LIEVE.

Methods: Males aged 18-65 who have hemophilia B (FIX ≤2%) and are receiving FIX prophylaxis are eligible to participate in B-LIEVE. Patients must be negative for AAVS3 neutralizing antibodies and have no history of FIX inhibitors. The dose for the first cohort of three patients in B-LIEVE is 7.7e11 vg/kg with a dose cap at 90 kg. Prophylactic immune management to prevent vector-related transaminitis consists of a tapering course of corticosteroids concurrent with a short course of tacrolimus. Up to six additional patients can be treated based on dose-adjustment requirements.

Results: Safety data and FIX levels for the first cohort treated in B-LIEVE will be presented.

Conclusion(s): Sustained FIX expression in the normal range is an important therapeutic goal for hemophilia B gene therapy. We will present results from B-LIEVE, a Phase 1/2 study of FLT180a designed to confirm the dose and immune management approach that consistently enables FIX expression within the normal range.