Sunday, February 9, 2025

Hemophilia A Breakthrough as NEJM Publishes Landmark Results from XTEND-Kids Phase 3 Study

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The New England Journal of Medicine (NEJM) has published full results from the XTEND-Kids phase 3 study on hemophilia A treatment, highlighting the efficacy, safety, and pharmacokinetic profile of ALTUVIIIO [Antihemophilic Factor (Recombinant), Fc-VWF-XTEN Fusion Protein]. ALTUVIIIO (efanesoctocog alfa) is a first-in-class, high-sustained factor VIII replacement therapy, approved for both adults and children with hemophilia A for routine prophylaxis, on-demand treatment to control bleeding episodes, and perioperative management (surgery). The study’s publication marks a significant milestone in the potential transformation of hemophilia A treatment, particularly for children under 12.

Dr. Lynn Malec, Medical Director of the Comprehensive Center for Bleeding Disorders and Associate Investigator at The Versiti Blood Research Institute, and Associate Professor of Medicine and Pediatrics at The Medical College of Wisconsin, commented, “Children represent a population for which it has been historically difficult to achieve effective bleed prevention. These published results demonstrate an important breakthrough as we strive to optimize the standard of care. Achieving high-sustained factor activity with once-weekly dosing helps mitigate the need to make a tradeoff between the treatment burden of factor replacement therapy and efficacy, which we often witness in treating severe hemophilia.”

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Pivotal XTEND-Kids Study Results

The XTEND-Kids study published in NEJM shows that ALTUVIIIO met primary and secondary endpoints, including the occurrence of factor VIII inhibitors and annualized bleed rates (ABRs). The results indicate no inhibitor development to factor VIII was detected with ALTUVIIIO (0% [95% confidence interval (CI)] 0–5%). The median annualized bleed rate (ABR) was 0.00 (interquartile range [IQR]: 0.00-1.02), and the estimated mean (95% CI) ABR was 0.61 (0.42–0.90) in the study of 73 patients treated per protocol. In children, clearance of administered factor concentrates from the blood is greater than in adults, often necessitating injections 2-4 times per week using standard (SHL) or extended half-life (EHL) factor VIII products.

Prevention of joint bleeds is critical to maintaining joint health throughout life. Eighty-two percent of the children treated with once-weekly ALTUVIIIO had zero joint bleeds, demonstrating that ALTUVIIIO weekly prophylaxis has the potential to provide long-term preservation of joint health. This high level of efficacy is a significant step forward in improving the quality of life for children with hemophilia A.

Dr. Dietmar Berger, Global Head of Development and Chief Medical Officer at Sanofi, stated, “The XTEND-Kids data validate the connection between high-sustained factor activity levels and improved health outcomes, including joint health. Offering a treatment option that emphasizes effective bleed protection in children with hemophilia can help give families increased peace of mind when their loved ones participate in everyday activities. The results are a testament to our scientific expertise and commitment to redefining the standard of care for children living with hemophilia through ALTUVIIIO and our broader portfolio of hemophilia therapies.”

Hemophilia A

Safety and Tolerability Profile

ALTUVIIIO was well-tolerated in children, with no adverse events leading to treatment discontinuation. The most common treatment-emergent adverse events (>10%) were SARS-CoV-2 test positive, upper respiratory tract infection, and fever (pyrexia). No serious allergic reactions, anaphylaxis, or embolic or thrombotic events were reported. This favorable safety profile further supports the use of ALTUVIIIO as a viable and effective treatment option for children with severe hemophilia A.

ALTUVIIIO [Antihemophilic Factor (Recombinant), Fc-VWF-XTEN Fusion Protein] is a first-in-class high-sustained factor VIII therapy designed to extend protection from bleeds with once-weekly prophylactic dosing for adults and children with hemophilia A. In adults and adolescents, ALTUVIIIO has a 3 to 4-fold longer half-life relative to standard and extended half-life factor VIII products, providing high-sustained factor activity levels within the normal to near-normal range, allowing for once-weekly administration.

ALTUVIIIO is the first factor VIII therapy shown to break through the von Willebrand factor ceiling, which imposes a half-life limitation on earlier generation factor VIII therapies. ALTUVIIIO builds on the innovative Fc fusion technology by adding a region of von Willebrand factor and XTEN polypeptides to extend its time in circulation. Currently approved and marketed in the US, Taiwan, and Japan, ALTUVIIIO received European Commission approval on June 17, 2024, for treating and preventing bleeds and perioperative prophylaxis in hemophilia A under the name ALTUVOCT.

Clinical Trial Details

The XTEND-Kids study (NCT04759131) was an open-label, non-randomized interventional study of once-weekly ALTUVIIIO in previously treated patients younger than 12 years of age with severe hemophilia A. Patients (N=74) received once-weekly ALTUVIIIO (50 IU/kg) prophylaxis for 52 weeks. The primary endpoint was the occurrence of factor VIII inhibitors. Secondary endpoints included annualized bleed rates (ABR) of treated bleeds, bleed treatment, joint health, quality of life, perioperative management, pharmacokinetics, and safety. An ongoing extension study, XTEND-ed (NCT04644575), is evaluating the long-term safety and efficacy of ALTUVIIIO in previously treated patients with severe hemophilia A for up to four years.

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Hemophilia A is a rare condition in which the ability of a person’s blood to clot properly is impaired, leading to excessive and spontaneous bleeds into joints that can result in joint damage and chronic pain, potentially impacting the quality of life. Disease severity is determined by the level of clotting factor activity in a person’s blood, meaning there is a negative correlation between bleeding risk and factor activity levels.

Sobi and Sanofi collaborate on the development and commercialization of Alprolix and Elocta/Eloctate. The companies also collaborate on the development and commercialization of efanesoctocog alfa, known as ALTUVIIIO in the US, Taiwan, and Japan, and ALTUVOCT in Europe. Sobi has final development and commercialization rights in the Sobi territory (essentially Europe, North Africa, Russia, and most Middle Eastern markets), while Sanofi holds rights in North America and other regions excluding the Sobi territory.

 

Resource: Sanofi, July 17, 2024


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