Unmet needs despite standard-of-care prophylaxis in Hemophilia A: improved outcomes after switching to Efanesoctocog...

The ECHO (MR-004, No. DEC24-269) study provides a real-world evaluation of efanesoctocog alfa (efa), a first-in-class ultra-long-acting factor VIII (FVIII) concentrate, within the French compassionate access (CAA) framework. It aims to characterize the unmet medical needs leading to CAA requests and evaluate the hemostatic efficacy and biological monitoring of efa prophylaxis. This multicenter study included 50 hemophilia A patients (84% severe; median age 31 years), including nine with inhibitor history. While 54% switched from FVIII prophylaxis, 46% transitioned from emicizumab due to persistent breakthrough bleeding (88%) and complex multifactorial scenarios (76%). Over a median 9-month follow-up, weekly efa prophylaxis resulted in a significant 89% reduction in treated bleeds (p < 0.001) and an 85% reduction in joint bleeds (p < 0.001) for the total population. This clinical benefit remained consistent across exploratory subgroups, including for patients previously on emicizumab. No new-onset inhibitors occurred. Biologically, the median centralized day-7 trough level was 7 IU/dL using a drug-calibrated bovine chromogenic substrate assay (CSA, n=31). However, a significant discrepancy was observed in paired comparisons (n=18): local one-stage assays (OSAs) yielded a median of 14 IU/dL, compared to a centralized CSA median of 7 IU/dL (p < 0.001). Notably, this divergence occurred across various local reagents considered acceptable alternatives to Actin FSL for efa monitoring. In conclusion, efa effectively addresses complex unmet needs, including in emicizumab-treated patients. However, the discrepancy between results of local OSAs and drug-calibrated CSA highlights challenges in laboratory monitoring.