Novel ITI concept using Efasenoctocog alfa in a modified Atlanta Protocol – the Gephard protocol

Introduction Immune tolerance induction (ITI) remains the cornerstone in managing hemophilia A patients with VIII (FVIII) inhibitors. Conventional ITI regimens, such as the Bonn or Atlanta protocols, require prolonged high-dose FVIII exposure and are associated with substantial treatment burden, morbidity, and costs. Novel extended half-life FVIII (EHL-FVIII) molecules may allow modified strategies with reduced frequency, optimized pharmacokinetics, and improved patient adherence. We report the first clinical experience of a modified Atlanta protocol (Gephard (German Paediatric Haemophilia Research Database) – protocol) applying efanesoctocog alfa, a novel FVIII fusion protein with extended half-life and sustained activity in the presence of inhibitors. Method We report retrospective data from 5 children with severe hemophilia A and high-titer inhibitors (range 37-1236.84BE) with ITI with efanesoctocog alfa. Demographic data, clinical data on inhibitor levels, bleeding rates and outcomes were extracted from patient records. Results Since licensing of efanesoctocog alfa we identified five children (median age 5,8 years, range 3-9 years). Two patients were on an ITI approach with a recombinant factor VIII product and switched to an ITI with efanesoctocog alfa. Three children started their first ITI attempt with efanesoctocog alfa. All patient received a bleeding prophylaxis with emicizumab. ITI was started with efanesoctocog alfa with 50 IU/kg 3 times/week (3 patients), 2 times/week (1 patients) or once a week (1 patient). The mean observation time was 171 days (range 81-231 days). All patients showed a decrease of inhibitor levels and have not yet reached tolerance. All five patients tolerated the regimen without thromboembolic complications or allergic reactions so far. During the ITI none of the patients suffered from a spontaneous bleed, only in one patient a traumatic bleed occurred. Conclusion To our knowledge this is the first clinical experience using efanesoctocog alfa. So far, the results suggest that efanesoctocog alfa may allow a successful, save and less burdensome ITI in children with high-titer inhibitors. Longer half-life of efanesoctocog alfa might allow longer factor VIII exposure. Further prospective, multicenter studies are warranted to validate these findings and to define standardized dosing algorithms [ 1 ] [ 2 ] [ 3 ]. Publication History Article published online: 17 February 2026 © 2026. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany