Clinical experience with efanesoctocog alfa in patients with uncover needs on emicizumab

Abstract Introduction Despite therapeutic advances, hemophilia A (HA) remains associated with joint bleeding, severe hemophilic arthropathy (AHS), and surgical complications. Real-world data indicate that some patients treated with emicizumab require factor VIII (FVIII) concentrates to control bleeding, arthropathy, and associated pain, as well as during surgical interventions. Efanesoctocog alfa (Altuvoct®), a recombinant FVIII with an ultra-extended half-life, offers increased protection against bleeding, an optimized pharmacokinetic profile, and hemostatic control with the potential to reduce perioperative costs. Methods We present data from four adult male patients with HA (one moderate and three severe) from multiple centers. All had received emicizumab prophylaxis. Three patients had AHS, chronic pain, and recurrent use of additional FVIII; the fourth underwent total knee arthroplasty with high requirements for extended half-life FVIII to achieve adequate factor levels, resulting in increased economic expenditure. After a 4-week washout period from the last dose of emicizumab, efanesoctocog alfa (50 IU/kg weekly) was initiated to improve joint control, optimize postoperative hemostasis, and reduce costs. Results Treatment initiation was safe, with no inhibitors or thrombotic events observed. FVIII trough levels remained >10%, and peak levels reached 80–130%, consistent with clinical trial data, providing protection against spontaneous bleeding; no joint hemorrhages were documented during follow-up. The three patients with AHS reported a progressive reduction in pain and decreased need for analgesics; two discontinued chronic analgesia before three months. In the surgical patient, efanesoctocog alfa allowed higher FVIII levels during the postoperative period and throughout rehabilitation without hemorrhagic complications. It is important to note the challenge in monitoring patients switching from emicizumab to efanesoctocog alfa, as FVIII levels needed to be measured using chromogenic assays, which are less accessible in most hospitals, despite discontinuation of emicizumab months prior. Conclusions While emicizumab offers the convenience of subcutaneous administration, the need for more effective bleeding control, management of AHS, and the clinical and economic benefits of efanesoctocog alfa were prioritized. In these patients, efanesoctocog alfa improved hemostatic control and joint status in individuals with HA and unmet needs under emicizumab, without safety concerns. Longer follow-up is necessary to confirm these findings with additional data.