Lynn Malec, MD, Versiti Blood Research Institute and Medical College of Wisconsin, discusses results from the XTEND-ed clinical trial evaluating efanesoctocog alfa for the treatment of patients with hemophilia A.
Hemophilia A is an inherited bleeding disorder in which the blood does not clot normally. People with hemophilia A will bleed more than normal after an injury, surgery, or dental procedure. Bleeding into the joints, muscles, brain, or organs can cause pain and other serious complications. Hemophilia A is caused by changes in the F8 gene that results in low levels of factor VIII, needed to form blood clots. .
Efanesoctocog alfa is a first-in-class high-sustained factor VIII replacement therapy designed to decouple recombinant factor VIII from endogenous von Willebrand factor. A third interim analysis of the XTEND-ed (NCT04644575) long-term extension study examining the safety and efficacy of efanesoctocog alfa prophylaxis in patients with severe hemophilia A was presented at the 2025 American Society of Hematology meeting.
In the extension study. patients who completed XTEND-1 (patients 12 years or older) and XTEND-Kids (patients younger than 12 years) were given the option to continue once-weekly 50 IU/kg efanesoctocog alfa prophylaxis in the ongoing, multicenter, open-label, long-term XTEND-ed study.
XTEND-1 to XTEND-ed
A total of 146 adults rolled over from XTEND-1 to XTEND-ed baseline. The median treatment duration in XTEND-ed was 166 weeks. No factor VIII inhibitor development was observed. During XTEND-ed, the mean annualized bleed rate (ABR) for day 1 to month 12 was 0.70, months 12 to 24 was 0.62 and months 24 to 36 was 0.45, with 65.8%, 68.1%, and 78.0% of participants with zero bleeds, respectively. The mean model-based ABR for the efficacy period was 0.60 for overall treated bleeds, and 0.20 and 0.29 for spontaneous and traumatic bleeds, respectively. Of 252 treated bleeding episodes, 94.0% were resolved with 1 efanesoctocog alfa injection and participants rated the response excellent/good for 87.8% bleeds. The median weekly efanesoctocog alfa consumption was 51.6 IU/kg.
In total, 86.3% experienced 1 or more treatment-emergent adverse event, most commonly COVID-19, arthralgia, influenza, and nasopharyngitis. Two participants had 1 or more treatment-related adverse event (facial paralysis and reduced factor VIII levels); no treatment-related serious adverse events were reported. Treatment-emergent adverse events unrelated to efanesoctocog alfa led to the death of two participants and treatment discontinuation in three participants.
XTEND-Kids to XTEND-ed
Among children, 71 rolled over from XTEND-Kids to XTEND-ed, with the median treatment duration of 116.7 weeks. No factor VIII inhibitors were observed. During XTEND-ed, the mean ABR evaluated for day 1 to month 12 was 0.68 and months 12 to 24 was 0.49, with 64.8% and 66.1% participants with zero bleeds, respectively. The mean model-based aABR was 0.64 for overall treated bleeds, and 0.08 and 0.44 for spontaneous and traumatic bleeds, respectively. Of 89 treated bleeding episodes, 91.0% were resolved with 1 efanesoctocog alfa injection and participants rated the response excellent/good for 94.1% bleeds. The median weekly efanesoctocog alfa consumption was 54.0 IU/kg.
Overall, 84.5% participants experienced 1 or more treatment-emergent adverse event, most commonly pyrexia, upper respiratory tract infection, arthralgia, and cough. Two participants had 1 or more treatment-related adverse event (asthma and post infusion pain and headache); no treatment-related serious adverse event or treatment discontinuations were reported.
For more information, click here.
To learn more about hemophilia and other rare hematologic conditions, visit https://checkrare.com/diseases/hematologic-disorders/