Researchers have discovered that valoctocogene roxaparvovec, an investigational adeno-associated virus serotype 5 (AAV5)-based factor VIII (FVIII) gene therapy for severe hemophilia A, provides sustained clinical benefits for patients over 4 to 5 years, according to a study published in Haemophilia.

Participants with severe hemophilia A experienced reduced annualized bleeding rate (ABR) and FVIII utilization, and hemostatic efficacy was sustained throughout the study period. Participants also reported a maintained or increased quality of life (QOL).

Patients with hemophilia A are usually treated with prophylactic FVIII replacement therapy or emicizumab. The goal of treatment is to reduce the frequency of bleeding, but patients with severe forms of hemophilia A still experience bleeds, which may be attributed to fluctuating levels of FVIII in replacement therapy. Valoctocogene roxaparvovec (AAV5-hFVIII-SQ) is a gene therapy developed to stabilize FVIII levels in the body.

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An ongoing study already has shown that it drastically reduces bleeding and eliminates the need for prophylactic FVIII replacement therapy for up to 3 years. Researchers thus set out to further investigate the benefits associated with this therapy in terms of safety, efficacy, tolerability, and QOL.

Researchers recruited 13 men aged 18 years and above with severe hemophilia A, defined as having FVIII ≤1 IU/dL. In addition, they possessed no anti-AAV5 antibodies and had no history of FVIII inhibitors or significant liver disease. Eligible participants were divided into 2 groups, each receiving 1 infusion of valoctocogene roxaparvovec of different dosages: the first received a dose of 6 × 1013 vg/kg (n=7), and the second received a dose of 4 × 1013 vg/kg dose (n=6). The first and second groups were followed up for 5 and 4 years, respectively.

Over the past 2 years, only a few adverse events were reported, with the most common being transient, mild-to-moderate alanine transaminase (ALT) elevations. No FVIII inhibitors were reported. At the fifth year of follow-up, 4 of 7 participants in the first group maintained median FVIII levels of <5 IU/dL, which corresponds to mild hemophilia, while 3 of 6 participants in the second group reported the same result at the fourth year of follow-up. No participants resumed prophylactic exogenous FVIII, and an impressive 8 of 13 participants reported no bleeding in the past 2 years.

Participants in the first group had an improved Haemo-QOL-A score from baseline at the fifth year of follow-up, while participants in the second group had a high baseline Haemo-QOL-A score that persisted when scored again at the fourth year of follow-up.

The results of this study illustrate the significant potential of gene therapy in creating a paradigm shift in the way hemophilia A is treated.


Pasi KJ, Laffan M, Rangarajan S, et al. Persistence of haemostatic response following gene therapy with valoctocogene roxaparvovec in severe haemophilia AHaemophilia. Published online August 11, 2021. doi:10.1111/hae.14391