NEJM publishes phase 3 data on ALTUVIIIO XTEND-Kids for severe hemophilia A in children

The New England Journal of Medicine (NEJM) has recently published comprehensive results from the XTEND-Kids phase 3 study, underscoring the efficacy and safety of ALTUVIIIO (efanesoctocog alfa) in children under 12 with severe hemophilia A. ALTUVIIIO is a pioneering factor VIII replacement therapy designed for routine prophylaxis, on-demand treatment to control bleeding episodes, and perioperative management.

Dr. Lynn Malec, Medical Director at the Comprehensive Center for Bleeding Disorders and Associate Professor at The Medical College of Wisconsin, emphasized the significance of these findings. Dr. Malec noted that achieving effective bleed prevention in children has historically been challenging. The data show that weekly dosing of ALTUVIIIO ensures high-sustained factor activity, addressing the trade-off often encountered between treatment burden and efficacy in severe hemophilia.

The XTEND-Kids study achieved its primary and secondary goals, observing no development of factor VIII inhibitors among participants. Specifically, the study reported an absence of inhibitor development (0% [95% CI 0–5%]) and a median annualized bleed rate (ABR) of 0.00 (IQR: 0.00-1.02). The estimated mean ABR was found to be 0.61 (95% CI 0.42–0.90) among the 73 patients treated according to protocol. Notably, pediatric patients usually require frequent injections (2-4 times weekly) using standard or extended half-life factor VIII products due to higher clearance rates of administered factor concentrates.

The study revealed that prevention of joint bleeds is crucial for maintaining joint health over a lifetime. Impressively, 82% of children treated with once-weekly ALTUVIIIO experienced no joint bleeds, highlighting its potential for long-term joint health preservation.

Dr. Dietmar Berger, Global Head of Development and Chief Medical Officer at Sanofi, acknowledged the study's contribution to understanding how high-sustained factor activity levels correlate with improved health outcomes, including joint health. Dr. Berger emphasized that effective bleed protection can provide families with peace of mind, particularly in allowing children to engage in everyday activities with minimal risk. He reinforced Sanofi's commitment to redefining the standard of care for hemophilia through ALTUVIIIO and other treatments in their portfolio.

ALTUVIIIO was well-tolerated among the pediatric participants, with no treatment discontinuations due to adverse events. Common adverse events (occurring in more than 10% of cases) included positive SARS-CoV-2 tests, upper respiratory tract infections, and fever. Importantly, there were no reports of severe allergic reactions, anaphylaxis, or thrombotic events.

ALTUVIIIO is an innovative high-sustained factor VIII therapy designed to extend bleed protection with once-weekly prophylactic dosing. In adults and adolescents, it provides sustained factor activity levels thanks to its longer half-life compared to standard therapies. ALTUVIIIO is the first therapy to surpass the von Willebrand factor ceiling, a limitation of previous generation factor VIII therapies. The therapy incorporates Fc fusion technology, von Willebrand factor, and XTEN polypeptides to extend its circulatory presence.

Currently, ALTUVIIIO is approved and marketed in the US, Taiwan, and Japan, and received approval from the European Commission under the name ALTUVOCT on June 17, 2024. It is noteworthy that ALTUVIIIO is the first factor VIII therapy to receive Breakthrough Therapy Designation from the US FDA in May 2022, alongside other designations such as Fast Track and Orphan Drug.

The XTEND-Kids study (NCT04759131) was an open-label, non-randomized interventional study involving once-weekly ALTUVIIIO in children under 12 with severe hemophilia A. Participants received ALTUVIIIO (50 IU/kg) weekly for 52 weeks. Primary endpoints included the occurrence of factor VIII inhibitors, while secondary endpoints encompassed ABR of treated bleeds, joint health, quality of life, and safety. An ongoing extension study, XTEND-ed (NCT04644575), is assessing the long-term safety and efficacy of ALTUVIIIO over four years.

Hemophilia A is a rare condition characterized by impaired blood clotting, leading to excessive bleeding and potential joint damage. The collaboration between Sobi and Sanofi focuses on developing and commercializing hemophilia treatments, including ALTUVIIIO in various global regions.