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A Leap Forward in Hemophilia A Treatment
Severe hemophilia A is conventionally treated with factor VIII concentrates, but effectiveness is limited by the von Willebrand factor (VWF)–imposed half-life ceiling, thereby requiring frequent infusions. Efanesoctocog alfa (ALTUVIIIO; formerly BIVV001) is designed to overcome this limitation by combining a recombinant factor VIII molecule with the Fc domain of human IgG1, the D′D3 domain of VWF, and two XTEN polypeptides.
XTEND-Kids, an international, industry-sponsored, open-label, phase 3 trial, evaluated the safety and efficacy of once-weekly intravenous (IV) efanesoctocog alfa (50 IU/kg) for 52 weeks in 74 children younger than age 12 with severe hemophilia A. All participants had >50 previous exposure days to factor VIII concentrates.
Factor VIII inhibitor development, the primary endpoint, was not observed in any participant. The median annualized bleeding rate (ABR) for treated bleeds was 0, indicating high therapeutic efficacy. Pharmacokinetic analysis after the first dose revealed sustained factor VIII activity with levels above 40 IU/dL for 3 days and above 10 IU/dL for ≈7 days. There was a trend towards improvement in health-related quality of life (HRQL), with modest improvement in joint health, particularly in older children. The treatment was generally well-tolerated, with no new safety concerns.
Comment
Although efanesoctocog alfa shows promise as a prophylactic option for previously treated children with severe hemophilia A, the study design has a notable flaw. The incidence of inhibitor development in previously treated patients is very low, making it an unsuitable primary endpoint for demonstrating the treatment's effectiveness in a real-world setting. Nevertheless, the study demonstrated important secondary outcomes, including a median ABR of 0 for treated bleeds and favorable pharmacokinetics. The long half-life and improved bleed protection with less-frequent dosing are significant advantages. However, challenges remain regarding IV administration and potential high costs, which could limit accessibility. Modest improvement in joint outcomes and HRQL suggest that efanesoctocog alfa is not transformative, as existing therapies have already made strides. The choice between efanesoctocog alfa and approved nonfactor therapies, such as emicizumab, may depend on patient preference, cost, and ability to manage IV versus subcutaneous administration.
Citation(s)
Author:
Malec L et al.
Title:
Efanesoctocog alfa prophylaxis for children with severe hemophilia A.
Source:
N Engl J Med
2024
Jul
18; [e-pub].
(Abstract/FREE Full Text)
Empfohlen von
Anjali A. Sharathkumar, MBBS, MD, MS