Abstract Number: PB1104
Meeting: ISTH 2020 Congress
Background: Clinical trials evaluating gene transfer for hemophilia B (HemB) have shown endogenous factor IX (FIX) expression in severe patients, changing their phenotype to mild/moderate or normal with a decrease in annual bleeding rate and factor usage and improvements in quality of life.
Aims: Here we report a case of unplanned orthopedic surgery in a patient with severe HemB treated with etranacogene dezaparvovec (AMT-061), an investigational gene therapy for HemB comprising an adeno-associated virus serotype 5 vector containing a codon-optimized Padua variant human FIX gene, with liver-specific promoter.
Methods: Retrospective chart review of a patient with severe HemB enrolled in a phase 2b trial of etranacogene dezaparvovec (NCT03489291) who underwent surgery.
Results: A 47 year old male with severe HemB with pre-existing stable bilateral femoral head avascular necrosis received a single intravenous dose of etranacogene dezaparvovec (2×1013 gc/kg). At week 21 the patient reported increasing bilateral hip pain, deemed unrelated to etranacogene dezaparvovec. At week 28 he was hospitalized for surgical bilateral femoral head coring. Immediately prior to surgery he was treated, per trial protocol, with recombinant FIX (BeneFIX) 3710U (50U/kg) and 1695U (25U/kg) at 24 hours postoperative. After discharge self-administered doses (25U/kg) of BeneFIX were administered (2000U at 48 and 72hrs; 1930U at 96 hours). There were no reports of bleeds, thrombosis or other complications related to this procedure. Endogenous FIX activity at the most proximal timepoints assessed pre-surgery (week 26) and post-surgery (week 36) were 57.0% and 50.9% respectively and ranged from 51.2% at week 12 to 40.8% at week 52.
Conclusions: Gene therapy with etranacogene dezaparvovec has potential to change the phenotype of patients with severe HemB allowing a decrease or elimination of infused FIX during surgical intervention. This report demonstrates safe reduced intensity and dose FIX supplementation in the context of surgery following HemB gene therapy.
To cite this abstract in AMA style:Giermasz A, Lickorish D, Sawyer E, Gut R, Gomez E. Surgical Management of a Hemophilia B Gene Transfer Clinical Trial Participant: A Case Report Following Etranacogene Dezaparvovec (AMT-061) Gene Therapy [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/surgical-management-of-a-hemophilia-b-gene-transfer-clinical-trial-participant-a-case-report-following-etranacogene-dezaparvovec-amt-061-gene-therapy/. Accessed October 1, 2023.
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