PMID- 38532939 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20240328 IS - 2512-9465 (Electronic) IS - 2567-3459 (Print) IS - 2512-9465 (Linking) VI - 8 IP - 1 DP - 2024 Jan TI - Safety and Efficacy of Recombinant Fusion Protein Linking Coagulation Factor IX with Albumin (rIX-FP) in Previously Untreated Patients with Hemophilia B. PG - e155-e163 LID - 10.1055/s-0044-1781466 [doi] AB - Introduction Recombinant fusion protein linking coagulation factor IX (FIX) with albumin (rIX-FP) has been shown to be an effective, well-tolerated treatment for patients with severe hemophilia B who had previously received factor replacement therapy. This study investigated the safety and efficacy of rIX-FP in previously untreated patients (PUPs). Methods Patients with moderately severe/severe hemophilia B (/=50 exposure days (EDs). Primary outcomes were the number of patients who developed FIX inhibitors and mean incremental recovery (IR) following a 50 IU/kg dose of rIX-FP. Secondary outcomes included incidence of adverse events (AEs) and annualized bleeding rates (ABRs). Results In total, 12 PUPs with a median age of 0 years (range, 0-11 years) were treated with rIX-FP for a median of 50 EDs (6/12 prophylaxis; 6/12 on-demand then prophylaxis). Overall, 11/12 patients did not develop FIX inhibitors; one 11-year-old patient developed an inhibitor against FIX after 8 EDs and was ultimately withdrawn. Mean (standard deviation) IR was 1.2 (0.4, n = 8) (IU/dL)/(IU/kg). Of the 137 treatment-emergent AEs recorded, five were attributed to rIX-FP. On the prophylaxis regimen, median ABR was 1.0 (range, 0-3.9, n = 12). No thromboembolic events or deaths occurred during the study. Conclusion This study provides data to support the safety and efficacy of rIX-FP in PUPs requiring on-demand or prophylactic treatment for moderately severe/severe hemophilia B, consistent with results in previously treated patients. Overall, 1/12 patients developed an inhibitor against FIX. CI - The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. ( https://creativecommons.org/licenses/by/4.0/ ). FAU - Lemons, Richard AU - Lemons R AD - Department of Pediatrics and Primary Children's Hospital, University of Utah, Salt Lake City, Utah, United States. FAU - Wang, Michael AU - Wang M AD - Hemophilia and Thrombosis Center, University of Colorado School of Medicine, Colorado, United States. FAU - Curtin, Julie AU - Curtin J AD - The Children's Hospital at Westmead, New South Wales, Australia. FAU - Lepatan, Lynda Mae AU - Lepatan LM AD - Department of Health Research and Pediatrics, Cebu Normal University-Vicente Sotto Memorial Medical Center College of Medicine, Cebu, Philippines. FAU - Male, Christoph AU - Male C AD - Department of Paediatrics, Medical University of Vienna, Vienna, Austria. FAU - Peyvandi, Flora AU - Peyvandi F AD - Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Milan, Italy. AD - Department of Pathophysiology and Transplantation, Universita degli Studi di Milano, Milan, Italy. FAU - von Depka Prondzinski, Mario AU - von Depka Prondzinski M AD - Werlhof Institute, Hannover, Germany. FAU - Wang, Rongrong AU - Wang R AD - CSL Behring, King of Prussia, Pennsylvania, United States. FAU - McKeand, William AU - McKeand W AD - CSL Behring, King of Prussia, Pennsylvania, United States. FAU - Seifert, Wilfried AU - Seifert W AD - CSL Behring, Marburg, Germany. FAU - Oldenburg, Johannes AU - Oldenburg J AD - Institute of Experimental Hematology and Transfusion Medicine, University Hospital Bonn, Medical Faculty, University of Bonn, Bonn, Germany. LA - eng PT - Journal Article DEP - 20240326 PL - Germany TA - TH Open JT - TH open : companion journal to thrombosis and haemostasis JID - 101715740 PMC - PMC10965291 OTO - NOTNLM OT - factor IX OT - hemophilia B OT - pediatric OT - previously untreated patients OT - prophylaxis COIS- Conflicts of Interest R.L. has received payment or honoraria from CSL Behring and has participated in a data safety monitoring board or advisory board for CSL Behring. M.W. has received clinical trial contracts from Bayer, BioMarin, Bioverativ/Sanofi, CSL Behring, Genentech/Roche, Novo Nordisk, Pfizer, Takeda, and uniQure; and participated in advisory boards for Bayer, Bioverativ/Sanofi, CSL Behring, Genentech/Roche, Hema Biologics/LFB, Novo Nordisk, and Takeda. J.C. reports study sponsorship from Bioverativ; research funding from CSL Behring and Shire/Takeda; personal fees from Bioverativ, CSL Behring, Pfizer, Roche, and Sanofi; hemophilia treatment center funding and equipment support from Pfizer; and advisory board participation for BioMarin, CSL Behring, Freeline, Novo Nordisk, Roche, Sanofi, and Shire/Takeda L.M.L. has participated in an advisory board for Pfizer and is an advisor of a local hemophilia support group "Hemophilia Association of the Phillipines, Inc." C.M. has received grants from Biotest and CSL Behring, and fees for study participation from Bayer, Biotest, CSL Behring, Novo Nordisk, Sobi, and Takeda. F.P. has received consulting fees from CSL Behring, Biomarin, Roche, Sanofi, and Sobi; payment or honoraria from Takeda/Spark; and has participated in data safety monitoring or advisory boards for CSL Behring, Biomarin, Roche, Sanofi, and Sobi. M.vDP. has received grants/research support from Baxter, Bayer, Biotest, CSL Behring, Octapharma, and Pfizer; consultancy fees from Baxter, Bayer, Biotest, CSL Behring, Novo Nordisk, Octapharma, Pfizer, Roche and Swedish Orphan Biovitrum; speaker bureau from Baxter, Bayer, Biotest, CSL Behring, Grifols, Novo Nordisk, Octapharma, Pfizer, and Swedish Orphan Biovitrum. R.W. is employed by and owns stocks in CSL Behring. W.M. is employed by and owns stocks in CSL Behring. W.S. is employed by CSL Behring. J.O. has received grants or contracts and support for attending meetings and/or travel and has participated on a data safety monitoring board or advisory board from/for Bayer, Biogen, Biomarin, Biotest, CSL Behring, Chugai, Freeline, Grifols, LFB, Novo Nordisk, Octapharma, Pfizer, Roche, Sanofi, Spark Therapeutics, Swedish Orphan Biovitrum, and Takeda; held voluntary roles at GTH and the foundation "Hamotherapie Forschung"; received equipment from Bayer (to the institution) and is employed by the University Clinic Bonn. EDAT- 2024/03/27 06:44 MHDA- 2024/03/27 06:45 PMCR- 2024/03/01 CRDT- 2024/03/27 03:49 PHST- 2023/08/14 00:00 [received] PHST- 2024/01/31 00:00 [accepted] PHST- 2024/03/27 06:45 [medline] PHST- 2024/03/27 06:44 [pubmed] PHST- 2024/03/27 03:49 [entrez] PHST- 2024/03/01 00:00 [pmc-release] AID - THOpen-24-01-0003 [pii] AID - 10.1055/s-0044-1781466 [doi] PST - epublish SO - TH Open. 2024 Mar 26;8(1):e155-e163. doi: 10.1055/s-0044-1781466. eCollection 2024 Jan.