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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

1Christian Medical College, Vellore, India, Vellore, Tamil Nadu, India, 2Beijing Children’s Hospital, Beijing, Beijing, China (People's Republic), 3Department of Pediatrics, Daejeon Eulji Medical Center, Eulji University School of Medicine, Daejeon, South Korea, Daejeon, Ch'ungch'ong-namdo, Republic of Korea, 4Department of Hematology, Ege University Faculty of Medicine, Children's Hospital, Izmir, Turkey, Izmir, Izmir, Turkey, 5Sanofi Genzyme, Chilly-Mazarin, France, Chilly-Mazarin, Ile-de-France, France, 6Sanofi Genzyme, São Paulo, Brazil, São Paulo, Sao Paulo, Brazil, 7Sanofi, Bridgewater, NJ, USA, Bridgewater, New Jersey, United States, 8Sanofi Genzyme, Cambridge, MA, USA, Cambridge, Massachusetts, United States, 9Sanofi, Cambridge, MA, USA, Cambridge, Massachusetts, United States, 10University of Michigan, Ann Arbor, Michigan, United States

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.

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