Altuviiio Shows Sustained Protection Against Bleeding Episodes in Children with Severe Hemophilia A

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Results from the Phase III XTEND-Kids trial (NCT04759131) found that once-weekly Altuviiio (efanesoctocog alfa) produced high sustained factor VIII activity and provided effective protection against bleeding episodes in children with severe hemophilia A, according to data from the trial published in The New England Journal of Medicine.^1,2 Altuviiio, a first-in-class, high-sustained factor VIII replacement therapy, was approved by the FDA in February 2023 for routine prophylaxis and on-demand treatment to control bleeding episodes, as well as for perioperative management in adults and children with hemophilia A.³

“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,” said Dietmar Berger, MD, PhD, global head of Development and chief medical officer at Sanofi, in a press release. “The results are a testament to our scientific expertise and commitment to redefine the standard of care for children living with hemophilia through Altuviiio and our broader portfolio of hemophilia therapies.”⁴

The open-label, international, single-group XTEND-Kids trial enrolled previously treated children under 12 years of age with severe hemophilia A. Eligibility requirements included administration of recombinantor plasma-derived factor VIII or cryoprecipitate for at least 150 exposure days in patients aged 6 to 12 years or for more than 50 exposure days in patients under 6 years of age.

Patients were administered once-weekly prophylactic doses of Altuviiio via intravenous (IV) infusion at a dose of 50 IU per kilogram for 52 weeks. Patients experiencing bleeding episodes were administered one 50 IU per kilogram dose of Altuviiio with additional doses of 30 or 50 IU per kilogram every two to three days if the episode did not resolve as determined by the caregiver after consulting with a trial investigator.

The trial’s primary endpoint was occurrence of inhibitor development with secondary endpoints that included annualized rate of treated bleeding episodes and annualized bleeding rate as per type and location; number of injections and doses of Altuviiio to treat a bleeding episode; percentage of bleeding episodes treated with one injection; evaluation of treatment response to individual bleeding episodes; annualized consumption of Altuviiio; perioperative management; joint health; target-joint resolution; pharmacokinetics; and safety. In total, 74 male patients were enrolled in the trial, of whom 38 were under 6 years of age and 36 were aged between 6 and 12 years.

Investigators found that factor VIII inhibitors did not develop. Among 73 patients treated as per protocol, median and model-based mean annualized bleeding rates were 0.00 (interquartile range, 0.00 to 1.02) and 0.61 (95% confidence interval, 0.42 to 0.90), respectively. Forty-seven patients did not experience a bleeding episode that required treatment, 65 patients did not have any spontaneous bleeding episodes, and 61 patients did not have any episodes of bleeding into joints. Further, 41 of 43 bleeding episodes were able to be resolved with a single IV injection of Altuviiio.

In terms of safety, most adverse events were reported as nonserious.

“The results of the XTEND-Kids study were consistent with those of XTEND-1, a phase III study of [Altuviiio] in previously treated adults and adolescents (≥12 years of age) with severe hemophilia A, in which the same weekly dose of 50 IU per kilogram was used, except for the 11-year-old outlier patient who was removed for ad hoc sensitivity analyses. Of note, the prolonged and intense treatment did not raise safety concerns,” the study authors wrote.¹

An ongoing extension study, XTEND-ed (NCT04644575) is continuing to evaluate the long-term safety and efficacy of Altuviiio in patients who were previously treated for severe hemophilia A for up to four years.

“Children represent a population for which it has been historically difficult to achieve effective bleed prevention and these published results demonstrate an important breakthrough as we strive to optimize the standard of care,” Lynn Malec, MD, medical director of Comprehensive Center for Bleeding Disorders, associate investigator at The Versiti Blood Research Institute, and associate professor of Medicine and Pediatrics at The Medical College of Wisconsin, said in the release. “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.”⁴

References

1. Efanesoctocog Alfa Prophylaxis for Children with Severe Hemophilia A. N Engl J Med 2024;391:235-246. DOI: 10.1056/NEJMoa2312611. Vol. 391 No. 3.

2. Safety, Efficacy and PK of BIVV001 in Pediatric Patients With Hemophilia A (XTEND-Kids). ClinicalTrials.gov. February 13, 2024. https://clinicaltrials.gov/study/NCT04759131

3. FDA approves once-weekly ALTUVIIIO™, a new class of factor VIII therapy for hemophilia A that offers significant bleed protection. Sanofi. News release. https://www.news.sanofi.us/2023-02-23-FDA-approves-once-weekly-ALTUVIIIO-TM-,-a-new-class-of-factor-VIII-therapy-for-hemophilia-A-that-offers-significant-bleed-protection. Published February 23, 2023. Accessed July 18, 2024.

4. NEJM publishes ALTUVIIIO XTEND-Kids phase 3 data supporting its potential to transform the treatment landscape for children with severe hemophilia A. Sanofi. News release. Published July 17, 2024. Accessed July 18, 2024. https://www.news.sanofi.us/2024-07-17-NEJM-publishes-ALTUVIIIO-XTEND-Kids-phase-3-data-supporting-its-potential-to-transform-the-treatment-landscape-for-children-with-severe-hemophilia-A