The Food and Drug Administration (FDA) has approved Altuviiio™ (antihemophilic factor [recombinant], Fc-VWF-XTEN fusion protein-ehtl), a first-in-class, high-sustained factor VIII (FVIII) replacement therapy.
Altuviiio is indicated for adults and children with hemophilia A (congenital factor VIII deficiency) for: routine prophylaxis to reduce the frequency of bleeding episodes; on-demand treatment and control of bleeding episodes; and perioperative management of bleeding. The novel recombinant FVIII therapy is designed to extend protection from bleeds by breaking the von Willebrand factor ceiling, which imposes a half-life limitation on current FVIII treatments.
The approval was based on data from the multicenter, open-label, nonrandomized, interventional phase 3 XTEND-1 study (ClinicalTrials.gov Identifier: NCT04161495), which evaluated the efficacy and safety of Altuviiio in patients 12 years of age and older with severe hemophilia A previously treated with FVIII replacement therapy.
The study included 2 parallel treatment arms: the prophylaxis Arm A (n=128), where patients received a weekly prophylactic 50 IU/kg dose of Altuviiio intravenously (IV) for 52 weeks; and the on-demand Arm B (n=26), where patients received on-demand treatment at doses of 50 IU/kg for 26 weeks, followed by weekly prophylaxis for 26 weeks.
Findings showed that weekly prophylactic treatment with Altuviiio resulted in clinically meaningful prevention of bleeds over 52 weeks; the median annualized bleeding rate (ABR) was 0 with a mean ABR of 0.70. An intra-patient comparison demonstrated a significant 77% (95% CI, 58-87) reduction in ABR with Altuviiio vs prior prophylactic FVIII replacement therapy. Additionally, patients with target joints at baseline (defined as ≥3 spontaneous bleeding episodes in a major joint which occurred in a consecutive 6-month period) achieved 100% resolution with 12 months of prophylactic treatment with Altuviiio.
In XTEND-1, there were a total of 362 bleeding episodes treated with Altuviiio. Bleeding was resolved with a single 50 IU/kg injection in 96.7% of bleeding episodes. Perioperative hemostasis was evaluated in 13 major and 22 minor surgeries. Treatment with Altuviiio was rated as “excellent” in all of these surgeries. As for safety, the most common adverse reactions reported were headache and arthralgia.
The efficacy of weekly Altuviiio as routine prophylaxis was also evaluated in pediatric patients less than 12 years of age (N=67; XTEND-Kids [ClinicalTrials.gov Identifier: NCT04759131]). Patients received Altuviiio 50 IU/kg IV once weekly for 52 weeks. An interim analysis showed that among patients who received routine prophylaxis for 26 weeks (n=23), the mean ABR was 0.5 and the median ABR was 0 for treated bleeds.
“This approval marks an important clinical advancement for the hemophilia community because we have an option that can achieve higher levels of factor activity with a single simplified weekly dose,” said Lynn Malec, MD, Medical Director of 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. “By maintaining high levels of factor activity throughout the week, patients can be confident in the bleed protection Altuviiio offers.”
Altuviiio is supplied in kits with a single-dose vial containing 250, 500, 750, 1000, 2000, 3000 or 4000 IU of factor VIII potency, a prefilled syringe, and a sterile vial adapter. The product is expected to be available in April 2023.
- Press release: FDA approves once-weekly Altuviiio™, a new class of factor VIII therapy for hemophilia A that offers significant bleed protection. News release. Sanofi-Aventis Groupe. Accessed February 23, 2023. https://www.globenewswire.com/news-release/2023/02/23/2614759/0/en/Press-Release-FDA-approves-once-weekly-ALTUVIIIO-a-new-class-of-factor-VIII-therapy-for-hemophilia-A-that-offers-significant-bleed-protection.html.
- Altuviiio. Package insert. Sanofi-Aventis Groupe; 2023. Accessed February 23, 2023. https://www.fda.gov/media/165594/download.