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Management of Infusion Reactions: Lessons from the Phase 3 HOPE-B Gene Therapy Trial of Etranacogene Dezaparvovec in Adults with Hemophilia B

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

Abstract Number: PB0659

Meeting: ISTH 2021 Congress

Theme: Hemophilia and Rare Bleeding Disorders » Hemophilia Gene Therapy

Background: The Phase 3 HOPE-B trial (NCT03569891) utilized etranacogene dezaparvovec, 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.

Aims: Here, adverse events of special interest reported as related to the investigational drug occurring on day of dosing are described.

Methods: Following a lead-in period of ≥6 months, 54 adult males with HB (FIX≤2%) with or without neutralizing antibodies (NAbs) to AAV5 received a single dose of etranacogene dezaparvovec (2×1013gc/kg) and completed 26 weeks of follow up.

Results: Seven of 54 (13%) participants experienced a total of 9 infusion-related reactions. Of the 9 reactions, 5 were mild and 4 were moderate, and they occurred in participants with AAV5 NAbs at baseline (5/7; titer range 23-3212) and in those without (2/7). All events were reported on the day of infusion and most (8/9) resolved on the same day. The first occurrence (a moderate suspected hypersensitivity reaction) occurred after approximately 10% of the dose of etranacogene dezaparvovec was administered; the drug was withdrawn and the participant received intravenous corticosteroids and antihistamines. Subsequent occurrences were managed through a combination of temporarily interrupting or slowing the etranacogene dezaparvovec infusion and/or supportive treatment with steroids/antihistamines. Three mild reactions (e.g. hives, itchiness, headache and dizziness) in 3 participants required no supportive treatment; this included 1 participant with a baseline AAV5 NAb titer of 3212.  

Conclusions: Infusion-related reactions occurred in 7/54 participants (13%), regardless of the presence or absence of AAV5 NAbs, the majority of which were mild and resolved on the same day. Mild reactions were successfully managed by decreasing the infusion rate. Temporary infusion interruption, supportive treatment with antihistamines and steroids, and a subsequent slower infusion rate are recommended for moderate reactions.  

To cite this abstract in AMA style:

Recht M, Leebeek FW, Miesbach W, S Key N, Lattimore S, Castaman G, Sawyer EK, Cooper D, Colletta V, Pipe SW, HOPE-B Investigators . Management of Infusion Reactions: Lessons from the Phase 3 HOPE-B Gene Therapy Trial of Etranacogene Dezaparvovec in Adults with Hemophilia B [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/management-of-infusion-reactions-lessons-from-the-phase-3-hope-b-gene-therapy-trial-of-etranacogene-dezaparvovec-in-adults-with-hemophilia-b/. Accessed November 29, 2023.

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ISTH Congress Abstracts - https://abstracts.isth.org/abstract/management-of-infusion-reactions-lessons-from-the-phase-3-hope-b-gene-therapy-trial-of-etranacogene-dezaparvovec-in-adults-with-hemophilia-b/