Abstract Number: OC 67.1
Meeting: ISTH 2021 Congress
Background: Sustained clinical benefit has been demonstrated following a single dose of valoctocogene roxaparvovec, an investigational AAV5-FVIII-SQ gene therapy for severe hemophilia A. Safety, tolerability, clinical efficacy, and quality of life were previously reported up to 4 years after administration, but questions remain regarding outcomes over even longer durations.
Aims: To report safety, tolerability, and efficacy of valoctocogene roxaparvovec up to 5 years after administration among participants in a phase 1/2 clinical study.
Methods: Adult male participants with severe hemophilia A who had previously been treated with FVIII received a single intravenous dose of valoctocogene roxaparvovec at 6×1013 vg/kg (n = 7) or 4×1013 vg/kg (n = 6).
Results: Annualized bleeding rate declined from pretreatment mean by 95% at year 4 in the 6×1013 vg/kg cohort and 93% at year 3 in the 4×1013 vg/kg cohort. Median (interquartile range) FVIII activity levels per chromogenic substrate assay were 16.4 (9.2–29.5) IU/dL at year 4 (6×1013 vg/kg cohort; n = 6) and 7.9 (3.4–18.0) IU/dL at year 3 (4×1013 vg/kg cohort; n = 6), continuing the shallow decline seen previously (Figure 1).
All participants demonstrated clinically significant FVIII activity levels with reductions in bleeds and FVIII usage and remained off prophylaxis with FVIII concentrates (Figure 2).
After 4 years, safety remained favorable, with no inhibitor development and few adverse events. Updated, detailed safety, durability, and efficacy assessments from 5-year follow-up data from the 6×1013 vg/kg cohort and 4-year data from the 4×1013 vg/kg cohort will be shared at ISTH 2021 Congress.
Conclusions: Valoctocogene roxaparvovec gene therapy previously demonstrated hemostatic efficacy and a favorable safety profile over 4 years. The 5-year data reported at ISTH 2021 will build on these results to provide the most up-to-date, long-term follow-up data currently available for investigational use of AAV-mediated therapy for hemophilia A.
To cite this abstract in AMA style:Pasi K, Rangarajan S, M Robinson T, Lester W, Symington E, Madan B, Laffan M, Li M, Kim B, F Pierce G, Wong WY. Hemostatic Response is Maintained for up to 5 Years Following Treatment with Valoctocogene Roxaparvovec, an AAV5-hFVIII-SQ Gene Therapy for Severe Hemophilia A [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/hemostatic-response-is-maintained-for-up-to-5-years-following-treatment-with-valoctocogene-roxaparvovec-an-aav5-hfviii-sq-gene-therapy-for-severe-hemophilia-a/. Accessed November 27, 2021.
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