SAFETY AND EFFICACY OF THE FITUSIRAN ANTITHROMBIN-BASED DOSE REGIMEN IN PEOPLE WITH HEMOPHILIA A AND B BY AGE GROUP
5 affiliations
- 1University of Southern California, Los Angeles, United States
- 2Joseph's Hospital Center for Bleeding and Clotting Disorders, Tampa, United States
- 33St. John's Medical College Hospital, Bengaluru, India
- 4Sanofi, United States
- 5Beijing Children’s Hospital and Capital Medical University, Beijing, China
Abstract
Introduction: Fitusiran is an antithrombin (AT)-lowering therapeutic that increases thrombin generation to restore hemostasis in people with hemophilia A and B (PwHA/B), with and without inhibitors. In the Phase 3 open-label extension study ATLAS-OLE (NCT03754790), the AT-based dose regimen (AT-DR; targeting AT levels of 15–35%) was well tolerated while maintaining clinically meaningful bleed protection. Objectives: To assess the safety and efficacy of fitusiran AT-DR in a subgroup analysis by age group. Methods: In ATLAS-OLE, males aged ≥12 years with severe HA/B, with and without inhibitors, received the AT-DR (starting dose 50 mg once every 2 months). The primary endpoint was safety and tolerability, assessed in all participants exposed to fitusiran. Key secondary endpoint was annualized bleeding rate (ABR) assessed during the primary efficacy period. Results: Overall, 286 participants (adolescent [12–17 years], n = 60; adult [18–64 years], n = 223; elderly [≥65 years], n = 3) were included in the safety analysis. The proportion of participants with any treatment-emergent adverse events (TEAEs; adolescents: 88.3%; adults: 81.6%; elderly: 100%) and serious adverse events (adolescents: 13.3%; adults: 14.3%; elderly: 33.3%) were similar, irrespective of age. Notably, there were no treatment discontinuations due to TEAEs in the adolescent and elderly populations. One of 60 (1.7%) adolescents, three of 223 (1.3%) adults and none of the elderly participants experienced a thrombotic event; no transaminase elevations >3x ULN were reported in adolescents nor in the elderly participants. Cholecystitis/cholelithiasis was reported in 5% of the adolescent, 3.6% of the adult, and none in elderly participants. Efficacy analyses were based on 213 participants (adolescent, n = 39; adult, n = 171; elderly, n = 3). The overall observed median (IQR) ABR was 3.7 (0.0, 7.5) (HA: 3.7 [0.0, 7.5]; HB: 3.7 [0.0, 11.2] Observed median (IQR) ABR were 3.7 (0.0, 11.2), 3.7 (0.0, 7.5), and 0 (0.0, 1.9) in the adolescent, adult, and elderly populations, respectively. A total of 40% of adolescents had no bleeds compared to 28.9% of adults. ABR and number of bleeds were notably lower in the elderly population; however, the sample size remains too small to support definitive conclusions. Conclusions: A similar safety profile and clinically meaningful bleed control was observed in adolescents aged 12–17 years and in adults in ATLAS-OLE. These data indicate the suitability of fitusiran prophylaxis for bleeding control for all PwH, irrespective of age. Funding: Sanofi.
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BibTeX
@article{young2026safety,
title = {{SAFETY AND EFFICACY OF THE FITUSIRAN ANTITHROMBIN-BASED DOSE REGIMEN IN PEOPLE WITH HEMOPHILIA A AND B BY AGE GROUP}},
author = {Guy YOUNG and Erin COCKRELL and Alok SRIVASTAVA and Abhimanyu YARRAMANENI and Ahrim YOUN and Laurel MENAPACE and Runhui WU},
journal = {Hematology, Transfusion and Cell Therapy},
year = {2026},
month = oct,
doi = {10.1016/j.htct.2026.108043},
url = {https://doi.org/10.1016/j.htct.2026.108043},
note = {CC BY},
}
RIS
TY - JOUR
TI - SAFETY AND EFFICACY OF THE FITUSIRAN ANTITHROMBIN-BASED DOSE REGIMEN IN PEOPLE WITH HEMOPHILIA A AND B BY AGE GROUP
AU - Guy YOUNG
AU - Erin COCKRELL
AU - Alok SRIVASTAVA
AU - Abhimanyu YARRAMANENI
AU - Ahrim YOUN
AU - Laurel MENAPACE
AU - Runhui WU
PY - 2026
DA - 2026/10/23
JO - Hematology, Transfusion and Cell Therapy
DO - 10.1016/j.htct.2026.108043
UR - https://doi.org/10.1016/j.htct.2026.108043
AB - Introduction: Fitusiran is an antithrombin (AT)-lowering therapeutic that increases thrombin generation to restore hemostasis in people with hemophilia A and B (PwHA/B), with and without inhibitors. In the Phase 3 open-label extension study ATLAS-OLE (NCT03754790), the AT-based dose regimen (AT-DR; targeting AT levels of 15–35%) was well tolerated while maintaining clinically meaningful bleed protection. Objectives: To assess the safety and efficacy of fitusiran AT-DR in a subgroup analysis by age group. Methods: In ATLAS-OLE, males aged ≥12 years with severe HA/B, with and without inhibitors, received the AT-DR (starting dose 50 mg once every 2 months). The primary endpoint was safety and tolerability, assessed in all participants exposed to fitusiran. Key secondary endpoint was annualized bleeding rate (ABR) assessed during the primary efficacy period. Results: Overall, 286 participants (adolescent [12–17 years], n = 60; adult [18–64 years], n = 223; elderly [≥65 years], n = 3) were included in the safety analysis. The proportion of participants with any treatment-emergent adverse events (TEAEs; adolescents: 88.3%; adults: 81.6%; elderly: 100%) and serious adverse events (adolescents: 13.3%; adults: 14.3%; elderly: 33.3%) were similar, irrespective of age. Notably, there were no treatment discontinuations due to TEAEs in the adolescent and elderly populations. One of 60 (1.7%) adolescents, three of 223 (1.3%) adults and none of the elderly participants experienced a thrombotic event; no transaminase elevations >3x ULN were reported in adolescents nor in the elderly participants. Cholecystitis/cholelithiasis was reported in 5% of the adolescent, 3.6% of the adult, and none in elderly participants. Efficacy analyses were based on 213 participants (adolescent, n = 39; adult, n = 171; elderly, n = 3). The overall observed median (IQR) ABR was 3.7 (0.0, 7.5) (HA: 3.7 [0.0, 7.5]; HB: 3.7 [0.0, 11.2] Observed median (IQR) ABR were 3.7 (0.0, 11.2), 3.7 (0.0, 7.5), and 0 (0.0, 1.9) in the adolescent, adult, and elderly populations, respectively. A total of 40% of adolescents had no bleeds compared to 28.9% of adults. ABR and number of bleeds were notably lower in the elderly population; however, the sample size remains too small to support definitive conclusions. Conclusions: A similar safety profile and clinically meaningful bleed control was observed in adolescents aged 12–17 years and in adults in ATLAS-OLE. These data indicate the suitability of fitusiran prophylaxis for bleeding control for all PwH, irrespective of age. Funding: Sanofi.
SN - 2531-1379
SN - 2531-1387
ER -