Concizumab use in toddlers with hemophilia B and inhibitors real-world data from an international collaboration.

BACKGROUND

Hemophilia B (HB) with inhibitors presents a treatment challenge, particularly in young children who may also experience allergic reactions to factor (F)IX. Concizumab, an antitissue factor pathway inhibitor monoclonal antibody, is a novel subcutaneous prophylactic agent recently approved for patients aged ≥12 years. However, data on its use in young children remain limited.

OBJECTIVES

To assess the safety, efficacy, and dosing of prophylactic concizumab in children under 6 years old with severe HB and inhibitors using data from compassionate or off-label use in Europe, Israel, and the United States.

METHODS

This international retrospective cohort study included 5 children aged 0 to 6 years with severe HB (FIX <1%) and inhibitors (Bethesda units >0.6) who were treated with concizumab for at least 12 weeks. Clinical, genetic, laboratory, and thrombin generation data were collected and analyzed. Exclusion criteria included coagulopathies and enrollment in industry-sponsored trials.

RESULTS

All patients experienced allergic reactions to FIX and developed inhibitors at a median age of 15 months. Concizumab prophylaxis began at a median age of 21 months. Annualized bleeding rates after concizumab therapy ranged from 0 to 4, with only 2 patients experiencing spontaneous bleeds, both resolving after dose adjustments. No thrombotic events occurred. Thrombin generation improved significantly posttreatment, and FIX inhibitor levels declined without additional FIX exposure or immune tolerance induction.

CONCLUSION

Concizumab appears safe and effective in young children with severe HB and inhibitors. It offers a promising, factor-free prophylactic strategy.