Abstract Number: OC 26.3
Meeting: ISTH 2021 Congress
Background: Gene therapy in hemophilia aims to provide long-term therapeutic benefit from a single administration.
Aims: The safety and efficacy of AMT-060, an adeno-associated virus serotype 5 (AAV5) vector with a codon-optimized wildtype human factor IX (FIX) gene and liver-specific promoter, was evaluated in 10 participants with severe/moderate-severe hemophilia B over 5 years (Phase 1/2 study, NCT02396342).
Methods: Adult males with FIX activity ≤2% and a severe bleeding phenotype received a single intravenous infusion of AMT-060 (5×1012 gc/kg, Cohort 1, n=5) or (2×1013 gc/kg, Cohort 2, n=5). Assessments included FIX activity, annualized bleeding rate (ABR), FIX replacement use, and treatment-related adverse events (TRAE).
Results: Mean FIX activity through 5 years was 5.2% in Cohort 1 (versus 4.4%; 6.8%; 7.3%; 7.0% through years 1-4 respectively) and 7.2% in Cohort 2 (versus 7.1%; 8.4%; 7.9%; 7.4% through years 1-4, respectively). Mean ABR during the last 12 and 6 months of observation was 6.5 for Cohort 1 and 0.0 for Cohort 2 (55% and 100% reduction vs. the year prior to treatment, respectively). In the same period, FIX replacement therapy consumption declined 84% (Cohort 1) and 99% (Cohort 2). All participants who discontinued prophylaxis remain prophylaxis-free through 5 years. No participants developed FIX inhibitors or signs of sustained AAV5 capsid-specific T-cell activation. TRAE were mainly reported in the first 3.5 months after treatment, including three cases of transient mild elevations in alanine aminotransferase. Final 5-year data will be presented.
Conclusions: Sustained endogenous FIX activity and reductions in ABR and use of FIX replacement were maintained through 5 years following a single administration of AMT-060, with no additional safety concerns. Participants are being offered enrolment in a long term follow up study over a further 5 years. Phase 3 study of the enhanced construct etranacogene dezaparvovec (AMT-061) is ongoing.
To cite this abstract in AMA style:Miesbach W, Meijer K, Coppens M, Kampmann P, Klamroth R, Schutgens R, Castaman G, K Sawyer E, WG Leebeek F. Five Year Data Confirms Stable FIX Expression and Sustained Reductions in Bleeding and Factor IX Use Following AMT-060 Gene Therapy in Adults with Severe or Moderate-severe Hemophilia B [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 1). https://abstracts.isth.org/abstract/five-year-data-confirms-stable-fix-expression-and-sustained-reductions-in-bleeding-and-factor-ix-use-following-amt-060-gene-therapy-in-adults-with-severe-or-moderate-severe-hemophilia-b/. Accessed September 24, 2021.
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