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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

1Phoenix Children's Hospital, Phoenix, United States, 2University of California Davis, Sacramento, United States, 3Azienda Ospedaliera Universitaria Careggi, Florence, Italy, 4University of North Carolina, Chapel Hill, United States, 5Oregon Health & Science University, Portland, United States, 6Erasmus University Medical Center, Rotterdam, Netherlands, 7University Hospital Frankfurt, Frankfurt, Germany, 8University of California San Diego, La Jolla, United States, 9uniQure Inc, Lexington, United States, 10University of Michigan, Ann Arbor, United States

Abstract Number: LPB0020

Meeting: ISTH 2021 Congress

Theme: Hemophilia and Rare Bleeding Disorders » Hemophilia Gene Therapy

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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