Factor VIII exposure, bleeding outcomes, and inhibitor development in 80 previously untreated patients and minimally treated patients with severe hemophilia A on emicizumab prophylaxis: real-world data from the PedNet Registry.

BACKGROUND

Subcutaneous emicizumab prophylaxis is increasingly used for early prophylaxis in infants with severe hemophilia A (SHA). Although the HAVEN 7 trial (NCT04431726) reported on 55 infants with SHA, real-world information regarding factor (F)VIII exposure, inhibitor development, and bleeding on this age group remains limited.

OBJECTIVES

To describe FVIII exposure, model-based annualized bleeding rate, and FVIII inhibitor development in infants with SHA starting emicizumab prophylaxis as previously untreated patients (PUPs) or minimally treated patients (MTPs; 1-5 FVIII-exposure days).

METHODS

Data on PUPs and MTPs with SHA on emicizumab for ≥12 weeks were extracted from the prospective, observational multicenter PedNet Registry on January 1, 2025, Participants in HAVEN 7 were excluded. FVIII exposure and inhibitor development were determined by survival analysis. Written informed consent was obtained from all parents/guardians.

RESULTS

This study included 80 infants (39 PUPs) starting emicizumab at a median of 8.6 months followed for a median of 19.5 months. During follow-up, 47/80 (59%) infants received FVIII for bleeding or concomitant prophylaxis (n = 10), with delayed first exposure at median 5.0 (MTPs) and 21.2 months (PUPs), respectively. The mean annualized bleeding rate was 0.6/year (95% CI, 0.4-1.1). Five infants (2 PUPs) developed FVIII inhibitors after 4 to 18 EDs, a cumulative incidence of 35.2% (95% CI, 8.6-61.7). No serious adverse events or thrombosis were reported.

CONCLUSION

These data show delayed FVIII exposure and good bleeding control without adverse events. Preliminary analysis suggested no decrease in FVIII inhibitor development. PedNet will continue to collect data needed to reliably assess the influence of different FVIII exposure during emicizumab prophylaxis on FVIII inhibitor development in PUPs.