Safety and Efficacy of the Fitusiran Antithrombin-based Dose Regimen in People With Hemophilia a and B by Age Group
Year: 2026
Type: article
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.
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W7223156345