Fitusiran prophylaxis in people with hemophilia A or B who switched from prior BPA/CFC prophylaxis: the ATLAS-PPX trial.

Autor:	Kenet G; The National Hemophilia Centre, Amalia Biron Thrombosis Research Institute, Sheba Medical Centre, Tel Hashomer, Tel Aviv University, Tel Aviv, Israel., Nolan B; Department of Hematology, Children's Health Ireland at Crumlin, Dublin, Ireland., Zulfikar B; Division of Pediatric Hematology-Oncology, Istanbul University Oncology Institute, Istanbul, Turkey., Antmen B; Department of Pediatric Hematology/Oncology and Bone Marrow Transplantation Unit, Faculty of Medicine, Acibadem University, Adana Hospital, Adana, Turkey., Kampmann P; Department of Hematology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark., Matsushita T; Department of Transfusion Medicine, Nagoya University Hospital, Nagoya, Japan., You CW; Department of Pediatrics, Daejeon Eulji Medical Center, Eulji University School of Medicine, Daejeon, South Korea., Vilchevska K; Department of Hematology, Ohmatdyt National Children's Specialized Hospital, Kyiv, Ukraine., Bagot CN; Department of Haematology, Glasgow Royal Infirmary, Glasgow, United Kingdom., Sharif A; Hospital Sultanah Aminah, Johor Bahru, Malaysia., Peyvandi F; Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Milan, Italy.; Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy., Young G; Hemostasis and Thrombosis Center, Cancer and Blood Diseases Institute, Children's Hospital Los Angeles, University of Southern California Keck School of Medicine, Los Angeles, CA., Negrier C; UR4609 Hemostasis and Thrombosis, Claude Bernard University Lyon 1, Lyon, France., Chi J; Sanofi, Bridgewater, NJ., Kittner B; Sanofi, Bridgewater, NJ., Sussebach C; Sanofi, Frankfurt, Germany., Shammas F; Sanofi, Montreal, Quebec, Canada., Mei B; Sanofi, Cambridge, MA., Andersson S; Sanofi, Cambridge, MA., Kavakli K; Department of Haematology, Ege University Faculty of Medicine, Children's Hospital, Izmir, Turkey.
Jazyk:	angličtina
Zdroj:	Blood [Blood] 2024 May 30; Vol. 143 (22), pp. 2256-2269.
DOI:	10.1182/blood.2023021864
Abstrakt:	Abstract: Fitusiran, a subcutaneous investigational small interfering RNA therapeutic, targets antithrombin to rebalance hemostasis in people with hemophilia A or B (PwHA/B), irrespective of inhibitor status. This phase 3, open-label study evaluated the efficacy and safety of fitusiran prophylaxis in males aged ≥12 years with hemophilia A or B, with or without inhibitors, who received prior bypassing agent (BPA)/clotting factor concentrate (CFC) prophylaxis. Participants continued their prior BPA/CFC prophylaxis for 6 months before switching to once-monthly 80 mg fitusiran prophylaxis for 7 months (onset and efficacy periods). Primary end point was annualized bleeding rate (ABR) in the BPA/CFC prophylaxis and fitusiran efficacy period. Secondary end points included spontaneous ABR (AsBR) and joint ABR (AjBR). Safety and tolerability were assessed. Of 80 enrolled participants, 65 (inhibitor, n = 19; noninhibitor, n = 46) were eligible for ABR analyses. Observed median ABRs were 6.5 (interquartile range [IQR], 2.2-19.6)/4.4 (IQR, 2.2-8.7) with BPA/CFC prophylaxis vs 0.0 (IQR, 0.0-0.0)/0.0 (IQR, 0.0-2.7) in the corresponding fitusiran efficacy period. Estimated mean ABRs were substantially reduced with fitusiran by 79.7% (P = .0021) and 46.4% (P = .0598) vs BPA/CFC prophylaxis, respectively. Forty-one participants (63.1%) experienced 0 treated bleeds with fitusiran vs 11 (16.9%) with BPAs/CFCs. Median AsBR and AjBR were both 2.2 with BPA/CFC prophylaxis and 0.0 in the fitusiran efficacy period. Two participants (3.0%) experienced suspected or confirmed thromboembolic events with fitusiran. Once-monthly fitusiran prophylaxis significantly reduced bleeding events vs BPA/CFC prophylaxis in PwHA/B, with or without inhibitors, and reported adverse events were generally consistent with previously identified risks of fitusiran. This trial was registered at www.ClinicalTrials.gov as #NCT03549871. (© 2024 American Society of Hematology. Published by Elsevier Inc. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)
Databáze:	MEDLINE
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