Abstract Number: OC 40.3
Meeting: ISTH 2022 Congress
Theme: Hemophilia and Rare Bleeding Disorders » Hemophilia - Clinical
Background: Fitusiran, an investigational siRNA prophylactic, targets antithrombin mRNA to rebalance haemostasis in people with haemophilia A or B (PwHA/B), irrespective of inhibitor status. For PwHA/B receiving fitusiran, reduced doses of on-demand clotting factor concentrates (CFC) or bypassing agents (BPA) are recommended to treat breakthrough bleeds.
Aims: To explore BPA/CFC consumption with fitusiran prophylaxis vs on-demand BPA/CFC in PwHA/B, with or without inhibitors.
Methods: Two randomised, open-label, Phase 3 trials (NCT03417102 and NCT03417245) enrolled males ≥12 years with severe haemophilia A/B with inhibitors (ATLAS-INH) and without (ATLAS-A/B). Eligible participants were randomised 2:1 to once-monthly 80 mg subcutaneous fitusiran or on-demand BPA (ATLAS-INH) or CFC (ATLAS-A/B) for 9 months. Annualised weight-adjusted BPA/CFC consumption, numbers of treated bleeds and infusions per bleed were assessed.
Results: Overall, 118 participants were randomised to fitusiran, 19 to on-demand BPA and 40 to on-demand CFC. Total consumption of aPCC and rFVIIa was 97.5% and 98.2% lower in the fitusiran arm vs on-demand BPA arm; overall mean consumption of FVIII and FIX was lower in the fitusiran arm vs on-demand CFC arm (95.9% and 94.7%, respectively) (Table 1). Total number of treated bleeds were lower in the fitusiran arm vs the on-demand BPA and CFC arms by 82.0% and 79.2%, respectively. In ATLAS-INH, participants who received fitusiran required fewer mean injections (1.2 vs 3.7) and lower mean BPA doses per bleed vs participants who received on-demand BPA (Table 2). In ATLAS-A/B, participants in both arms required a mean 1.2 injections per bleed; participants who received fitusiran required lower mean CFC doses vs participants who received on-demand CFC (Table 2).
Conclusion(s): Fitusiran prophylaxis reduced total BPA/CFC consumption by reducing number of treated bleeds, number of injections and BPA/CFC doses required to treat breakthrough bleeds in PwHA/B with and without inhibitors, by ~95% or more thereby reducing treatment burden.
To cite this abstract in AMA style:
Srivastava A, Wu R, You C, Kavakli K, Bartelt-Hofer J, Rosim R, Qiu Z, Cano V, Andersson S, Pipe S. Consumption of On-demand Factor Concentrates and Bypassing Agents for Management of Breakthrough Bleeds with Fitusiran Prophylaxis in People with Haemophilia A or B: An Analysis of Two Phase 3 Studies [abstract]. https://abstracts.isth.org/abstract/consumption-of-on-demand-factor-concentrates-and-bypassing-agents-for-management-of-breakthrough-bleeds-with-fitusiran-prophylaxis-in-people-with-haemophilia-a-or-b-an-analysis-of-two-phase-3-studies/. Accessed August 8, 2022.« Back to ISTH 2022 Congress
ISTH Congress Abstracts - https://abstracts.isth.org/abstract/consumption-of-on-demand-factor-concentrates-and-bypassing-agents-for-management-of-breakthrough-bleeds-with-fitusiran-prophylaxis-in-people-with-haemophilia-a-or-b-an-analysis-of-two-phase-3-studies/