Abstract Number: PB0653
Meeting: ISTH 2021 Congress
Background: The investigational gene therapy for hemophilia B (HB) etranacogene dezaparvovec comprises an adeno-associated virus serotype 5 (AAV5) vector containing a codon-optimized Padua variant human factor IX (FIX) transgene with a liver specific promoter.
Aims: A Phase 3 trial (HOPE-B; NCT03569891) is underway to further assess efficacy and safety of etranacogene dezaparvovec in adults with HB.
Methods: An open-label, single-dose, single-arm, international trial in adult males with severe or moderate-severe HB (FIX≤2%) on routine FIX prophylaxis and with/without pre-existing neutralizing antibodies (NAbs) to AAV5. A ≥6 month lead-in period preceded a single dose of etranacogene dezaparvovec (2×1013gc/kg). The co-primary endpoints were FIX activity at 26 and 52wks and 52wk annualized bleeding rate (ABR). Secondary endpoints included adverse events (AEs), and reactive use of steroids.
Results: 54pts were dosed and completed 26wks of follow-up. During lead-in, 38pts (70%) had 123 bleeds (42 spontaneous; 66 traumatic; 15 other), despite prophylaxis. Post treatment with etranacogene dezparvovec, at 26wks, mean (SD; min,max) change in FIX activity from BL was +36.0% (19.7; 0,96.1, p<0.0001) and 52/54 participants had successfully discontinued routine prophylaxis. 23/54 pts had pre-existing AAV5 NAbs; no correlation with FIX activity was seen up to a titer of 678.2; n=52, R2=0.078; one participant with a NAb titer of 3212.3 did not respond and an additional participant received a partial dose and remained on prophylaxis. Relative to lead–in, total bleeds reduced by 83% and treated bleeds reduced by 91% at 26wks. Treatment-related AEs occurred in 37 participants, most of which (81.5%) were mild. One year data on FIX activity, ABR, use of FIX replacement and safety will be presented.
Conclusions: Following a single dose of etranacogene dezaparvovec, FIX activity increased, without the need for prophylactic immunosuppression, into the mild-to-normal range at 26wks in pts with severe/moderately severe HB.
To cite this abstract in AMA style:W Pipe S, Leebeek FW, Recht M, S Key N, Lattimore S, Castaman G, K Sawyer E, Verweij S, Colletta V, Cooper D, Dolmetsch R, Miesbach W, HOPE-B Investigators . 52 Week Efficacy and Safety of Etranacogene Dezaparvovec in Adults with Severe or Moderate-severe Hemophilia B: Data from the Phase 3 HOPE-B Gene Therapy Trial [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/52-week-efficacy-and-safety-of-etranacogene-dezaparvovec-in-adults-with-severe-or-moderate-severe-hemophilia-b-data-from-the-phase-3-hope-b-gene-therapy-trial/. Accessed November 30, 2023.
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