Sanofi announced it will present new data from its hemophilia portfolio at the 32nd Congress of the International Society on Thrombosis and Haemostasis (ISTH), taking place June 22-26, 2024, in Bangkok, Thailand. Notable presentations on ALTUVIIIO [Antihemophilic Factor (Recombinant), Fc-VWF-XTEN Fusion Protein] include long-term interim phase 3 data on the efficacy and safety of the treatment in adults and children with severe hemophilia A. Abstracts on fitusiran include information on surgical experience as well as long-term safety data from the ATLAS phase 3 clinical development program in adults and adolescents with hemophilia A or B, regardless of inhibitor status. ALTUVIIIO: Interim analyses of XTEND-ed, a long-term extension phase 3 study, showed that in adult and pediatric populations, the use of ALTUVIIIO continued to provide highly effective bleed prevention leading to improvement or maintenance of joint health over a two-year period, and a safety profile consistent with that reported in the initial studies.

The following abstracts will be presented at the meeting: ?First Interim Analysis of Clinical Outcomes in Adults and Adolescents With Severe Hemophilia A Receiving Efanesoctocog Alfa Prophylaxis in XTEND-ed, a Phase 3 Long-term Extension Study?: In previously treated patients (=12 years old) who had the completed the XTEND-1 (Arm A/B) trial, the mean annualized bleed rate (ABR) with ALTUVIIIO was 0.72 (standard deviation [SD])=1.26) for arm A and 0.42 (SD=0.89) for arm B. No factor VIII inhibitors were detected (abstract OC50.1). ?Interim Analysis of Joint Outcomes in Adult and Adolescent Patients with Severe Hemophilia A Receiving Efanesoctocog Alfa During the Phase 3 XTEND-ed Long-Term Extension Study?: In patients who continued to receive once weekly ALTUVIIIO (50 IU/kg) in XTEND-ed, joint health had improved or been maintained in adults and adolescents over a two-year period, as measured by Hemophilia Joint Health Score total score, total joint score, and subdomain scores (abstract OC01.4). ?Long-term Outcomes With Efanesoctocog Alfa Prophylaxis for Previously Treated Children With Severe Hemophilia A, an Interim Analysis of the Phase 3 XTEND-ed Study": No factor VIII inhibitors were detected.

The mean ABR was 0.70 (SD=1.27), a rate similar to the mean ABR observed in XTEND-Kids (abstract OC50.2). Additional data being presented at ISTH show that across clinical studies, ALTUVIIIO demonstrated effective bleed protection when used for perioperative management in participants with severe hemophilia A: ?Perioperative Management with Efanesoctocog Alfa in Adults, Adolescents, and Children with Severe Hemophilia A in the Phase 3 XTEND Clinical Program?: In 41 patients from the XTEND-1, XTEND-Kids, and XTEND-ed studies who underwent 49 major surgeries, hemostasis was maintained in all surgeries and hemostatic response with ALTUVIIIO was rated as excellent in most surgeries (43/49) (abstract OC14.1). Fitusiran: Additional analyses will be presented at ISTH that support the potential of fitusiran as a first-in-class treatment offering consistent bleed protection for patients with hemophilia A or B, regardless of inhibitor status.

Novel results on the perioperative management of hemophilia using fitusiran prophylaxis in the ATLAS clinical development program demonstrated that major surgeries can be safely performed in patients on fitusiran: ?Surgical experience in people with hemophilia A or B with and without inhibitors receiving fitusiran?: 60 major surgeries, including 24 in people with hemophilia with inhibitors, were conducted in the fitusiran clinical development program at the time of this analysis. Major surgeries were safely and effectively conducted with fitusiran prophylaxis following bleed management guidelines, irrespective of the patient?s inhibitor status (abstract OC14.2). Additional data presented at ISTH support the favorable safety profile for fitusiran and demonstrate that fitusiran prophylaxis under an antithrombin-based dosing regimen (AT-DR) successfully mitigated the risk of thrombotic events (TEs) and reduced the incidence of elevated liver enzymes and gallbladder inflammation or gallstones. The following abstracts will be presented at ISTH: ?Incidence of thrombotic events in the fitusiran clinical development program?: Fitusiran prophylaxis under an AT-DR led to a marked reduction in TEs with substantially greater exposure on the AT-DR (abstract OC40.2).  ?Hepatobiliary events in the fitusiran clinical development program with the revised AT-based dose regimen?: Fitusiran prophylaxis under an AT-DR led to reductions in liver transaminase elevations and cholecystitis/cholelithiasis events.

Liver transaminase elevations were infrequent and transient, and events of cholecystitis/cholelithiasis resolved without clinical complications with no fitusiran dose interruptions or discontinuations (abstract OC40.3). These presentations reinforce pivotal data that were presented earlier this year from the phase 3 open-label extension study (ATLAS-OLE) of fitusiran prophylaxis showing that maintaining AT activity levels between 15-35% resulted in clinically meaningful bleed control and a substantially improved benefit risk profile in people with hemophilia A or B, with or without inhibitors. Regulatory submissions for fitusiran for the treatment of hemophilia A or B in adults and adolescents with or without inhibitors have been completed in China, Brazil and the US with a US Food and Drug Administration (FDA) target action date of March 28, 2025.

The FDA also granted fitusiran Breakthrough Therapy Designation for hemophilia B with inhibitors in December 2023.