Stable and durable factor IX levels in hemophilia B patients over 3 years post etranacogene dezaparvovec gene therapy

Etranacogene dezaparvovec (AMT-061) is a recombinant adeno-associated virus serotype 5 (AAV5) vector containing a codon-optimized Padua variant human factor IX (FIX) transgene with a liver-specific promoter. Here we report 3-year outcomes from a Phase 2b, open-label, single-dose, single-arm, multi-center trial (NCT03489291) conducted in adults with severe or moderately severe hemophilia B (FIX ≤2%). All participants (n=3) received a single intravenous dose (2×1013 gene copies/kg) and will be followed for 5 years. The primary endpoint of FIX activity ≥5% at 6 weeks was met (mean 30.6% [min-max, 23.9%-37.8%]). Secondary endpoints included bleed frequency, FIX concentrate use, joint health, and adverse events (AEs). All participants required routine FIX prophylaxis and had neutralizing antibodies to AAV5 (mean titer at screening=39) prior to etranacogene dezaparvovec treatment. Post administration, FIX activity rose to a mean of 40.8% (min-max, 31.3%-50.2%) at year 1, sustained at year 3 (mean 36.9% [min-max, 32.3%-41.5%]). All participants discontinued FIX prophylaxis. Complete elimination of bleeds occurred in 2/3 participants. One participant required on-demand FIX replacement therapy post treatment per protocol due to elective surgeries, for 2 reported bleeding episodes, and twice for a single self-administered infusion due to an unreported reason. One participant experienced 2 mild, self-limiting AEs shortly after dosing. During the 3-year study period, there were no clinically significant elevations in liver enzymes, no requirement for steroids, no FIX inhibitor development, and no late emergent safety events in any participant. Etranacogene dezaparvovec was safe and effective in adults with hemophilia B through 3 years post-administration. ClinicalTrials.gov Identifier: NCT03489291.