Objective Gene therapy for hemophilia may improve disease severity to a mild or functionally curative state through a single administration. Etranacogene dezaparvovec (AMT-061) is an investigational gene therapy for hemophilia B comprising an adeno associated virus serotype 5 (AAV5) vector containing a codon-optimized Padua variant human factor IX (FIX) gene with liver specific promoter. We have previously shown a single dose of etranacogene dezaparvovec provides sustained FIX activity into the mild-to normal range up to 52 weeks in adults with severe or moderate-severe hemophilia B. Two years of follow-up data will be presented.
Material and Methods A Phase 2b, open-label, single-dose, single-arm, multi-center trial (NCT03489291) in adult hemophilia B subjects, who were not excluded based on neutralizing antibodies to AAV5. All subjects received a single intravenous dose of etranacogene dezaparvovec (2x10^13 gc/kg) and will be followed for 5-years. The primary endpoint was FIX activity at Week 6.
Results All participants had FIX ≤1 %, required routine FIX prophylaxis, and had neutralizing activity to AAV5 at baseline. Following treatment, FIX activity increased rapidly to a mean of 31 % at Week 6 and 41 % by Week 52, with FIX activity levels of 50 %, 31 % and 41 % in participants 1-3 respectively. There was no relationship between the presence of anti-AAV5 NAbs and response to treatment. As of 52 weeks, there were no bleeds post-treatment and no requirement for FIX replacement other than protocol specified use in participant 3. There were no clinically significant elevations in liver enzymes and no participants required steroids related to the treatment. One participant experienced 2 mild AEs possibly related to treatment shortly after dosing (self-limiting headache and slightly elevated CRP). Participant 3 underwent hip surgery deemed unrelated to treatment and received FIX per protocol according to standard clinical practice. No participant developed inhibitors to FIX.
Conclusion Patients with AAV5 NAbs were included in the Phase 2b etranacogene dezaparvovec trial and have shown sustained FIX activity into the mild-to normal range. All participants were able to discontinue routine prophylaxis, and there have been no bleeds post-treatment with etranacogene dezaparvovec.
