Abstract Number: OC 67.3
Meeting: ISTH 2021 Congress
Background: Etranacogene dezaparvovec is an investigational gene therapy for hemophilia B (HB) comprising an adeno-associated virus serotype 5 (AAV5) vector containing a codon-optimized Padua variant human factor IX (FIX) transgene with a liver specific promoter. Preliminary data suggest that anti-AAV5 neutralizing antibodies (NAbs) may not preclude successful transduction with etranacogene dezaparvovec.
Aims: A Phase 3 trial (HOPE-B; NCT03569891) was established to assess efficacy and safety of a single dose of etranacogene dezaparvovec (2×1013gc/kg).
Methods: Adult males with HB (FIX≤2%) receiving routine FIX prophylaxis, with/without AAV5 NAbs, were enrolled into this open-label, single-dose, single-arm trial, following a ≥6 month lead-in. Co-primary endpoints; change in FIX activity (measured by one stage assay) at 26 and 52wks and 52wk annualized bleeding rate compared to lead-in. Here, outcomes at 26wks are analyzed using descriptive statistics and a correlation analysis.
Results: 54 participants were dosed and completed 26wks of follow-up, 23 (42.6%) of whom had AAV5 Nabs at baseline (BL) with a median titer of 56.9 (max titer 3212; 1st-3rd quartile 23.3-282.5) and a distribution representative of the general population. One participant (titer 198) received a partial dose and was excluded from efficacy assessments. One participant (titer 3212) did not respond and remained on prophylaxis. All other participants (n=52) discontinued prophylaxis. No correlation of pre-existing NAbs with FIX activity was observed up to a titer of 678 (n=52, r=-0.28 [95% CI -0.51, 0.00], R2=0.078). Mean FIX activity at 26 weeks was 32.7 IU/dl (min <2, max 90.4, 1st-3rd quartile 16.3-42.6, n=22) in participants with NAbs versus 41.3 IU/dl (min 8.4, max 97.1, 1st-3rd quartile 31.3-52.7, n=31) in those without.
No deaths and no inhibitors to FIX were reported.
|Adverse event (n)||With AAv5 NAbs at
|Without AAv5 NAbs at baseline (n=31)|
|Transient transaminitis requiring corticosteroids||2/23||7/31|
Conclusions: This study demonstrates successful treatment of participants with generally prevalent titers of pre-existing NAbs to AAV5 with etranacogene dezaparvovec, supporting broad eligibility for AAV5-based therapies.
To cite this abstract in AMA style:Leebeek FW, Miesbach W, Recht M, S Key N, Lattimore S, Castaman G, K Sawyer E, Cooper D, Ferriera V, W Pipe S, HOPE-B Investigators . Clinical Outcomes in Adults with Hemophilia B with and without Pre-existing Neutralizing Antibodies to AAV5: 6 Month Data from the Phase 3 Etranacogene Dezaparvovec HOPE-B Gene Therapy Trial [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/clinical-outcomes-in-adults-with-hemophilia-b-with-and-without-pre-existing-neutralizing-antibodies-to-aav5-6-month-data-from-the-phase-3-etranacogene-dezaparvovec-hope-b-gene-therapy-trial/. Accessed July 1, 2022.
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