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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

1University of Michigan, Ann Arbor, United States, 2Erasmus University Medical Center, Rotterdam, Netherlands, 3Oregon Health & Science University, Portland, United States, 4University of North Carolina, Chapel Hill, United States, 5Center for Bleeding Disorders and Coagulation, Careggi University Hospital, Florence, Italy, 6uniQure Inc, Lexington, United States, 7uniQure BV, Amsterdam, Netherlands, 8University Hospital Frankfurt, Frankfurt, Germany

Abstract Number: PB0653

Meeting: ISTH 2021 Congress

Theme: Hemophilia and Rare Bleeding Disorders » Hemophilia Gene Therapy

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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