Abstract Number: LPB0020
Meeting: ISTH 2021 Congress
Background: Etranacogene dezaparvovec, an investigational gene therapy for hemophilia B (HB), comprises an adeno associated virus serotype 5 (AAV5) vector containing a codon-optimized Padua variant human factor IX (FIX) transgene with liver-specific promoter.
Aims: We previously demonstrated that a single dose of etranacogene dezaparvovec provides sustained FIX activity in the mild-to-normal range for up to two years. Updated results through 30 months of follow-up will be presented.
Methods: A Phase 2b, open-label, single-dose, single-arm, multi-center trial in adult HB participants (n=3). All participants received a single intravenous dose of etranacogene dezaparvovec (2×1013 gc/kg) and are being followed for 5-years. The primary endpoint was FIX activity at Week 6. Secondary endpoints include bleeds, use of FIX replacement, laboratory parameters, joint health, and adverse events (AEs) (NCT03489291).
Results: Participants had FIX ≤1%, required routine FIX prophylaxis, and had neutralizing antibodies to AAV5 at baseline. Following treatment with etranacogene dezaparvovec, FIX activity rapidly increased to a mean of 31% at Week 6. By 2 years, mean FIX activity further increased to 44.2%, with FIX activity levels of 45%, 36% and 52% in participants 1-3 respectively. No relationship between treatment response and presence of anti-AAV5 NAbs at BL was observed. One participant experienced a spontaneous mild bleed and self-administered a single infusion of FIX replacement in year 2. No clinically significant elevations in liver enzymes occurred and no participant required steroids related to treatment. As reported previously, one participant experienced 2 mild AEs possibly-related to treatment shortly after dosing and one participant underwent hip surgery. No participant developed inhibitors to FIX. Data up to 2.5 years will be presented.
Conclusions: Patients in this Phase 2b etranacogene dezaparvovec trial have shown sustained FIX activity into the mild-to normal range over 2 years, enabling discontinuation of routine prophylaxis, irrespective of neutralizing antibodies to AAV5 at baseline.
To cite this abstract in AMA style:Gomez E, Giermasz A, Castaman G, S Key N, U Lattimore S, Leebeek FW, Miesbach W, Recht M, von Drygalski A, K Sawyer E, Pipe SW. Etranacogene Dezaparvovec (AAV5-Padua hFIX Variant, AMT-061), an Enhanced Vector for Gene Transfer in Adults with Severe or Moderate-severe Hemophilia B: 2.5 Year Data from a Phase 2b Trial [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/etranacogene-dezaparvovec-aav5-padua-hfix-variant-amt-061-an-enhanced-vector-for-gene-transfer-in-adults-with-severe-or-moderate-severe-hemophilia-b-2-5-year-data-from-a-phase-2b-trial/. Accessed November 30, 2023.
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