Abstract Number: LB 01.1
Meeting: ISTH 2022 Congress
Theme: Hemophilia and Rare Bleeding Disorders » Hemophilia - Clinical
Background: Fitusiran, a subcutaneous (SC) investigational siRNA therapeutic, targets antithrombin to rebalance haemostasis in people with haemophilia A or B (PwHA/B), irrespective of inhibitor status. In previous Phase 3 trials, once-monthly fitusiran prophylaxis significantly reduced annualised bleeding rate (ABR) in PwHA/B, with or without inhibitors versus episodic/on-demand treatment.
Aims: To evaluate the efficacy and safety of fitusiran versus prior factor/bypassing agent (BPA) prophylaxis in PwHA/B, with or without inhibitors.
Methods: This Phase 3, multinational, open-label study (NCT03549871) included males aged ≥12 years with hemophilia A or B, with or without inhibitors, who had prior factor/BPA prophylaxis. Participants continued factor/BPA prophylaxis (6 months) before switching to once-monthly 80 mg SC fitusiran prophylaxis (7 months). Primary endpoint was ABR in the factor/BPA prophylaxis period (Day-168 to Day-1) and fitusiran efficacy period (Day 29 to Day 190). Secondary endpoints included spontaneous ABR (AsBR), joint ABR (AjBR), and health-related quality of life (HRQoL). Safety and tolerability were assessed.
Results: Of 80 enrolled participants, 65 (inhibitor/non-inhibitor, n=19/46; haemophilia A/haemophilia B, n=50/15) were eligible for ABR analyses. Median observed (IQR) ABRs were 4.4 (2.2; 10.9) with factor/BPA and 0.0 (0.0; 2.3) with fitusiran prophylaxis; 41 participants (63.1%) experienced zero treated bleeds with fitusiran. Fitusiran achieved statistically significant reductions in estimated ABR, AsBR and AjBR versus factor/BPA prophylaxis (Table 1). Fitusiran significantly improved HRQoL versus factor/BPA as measured by Haem-A-QOL total score (LS mean difference -4.6 [95% CI: -7.6; -1.5; p< 0.01]). Serious adverse events (SAEs) occurred in 5/65 participants (7.7%) with factor/BPA and 9/67 (13.4%) with fitusiran prophylaxis. Two participants (3.0%) experienced suspected or confirmed thromboembolic events with fitusiran (Table 2).
Conclusion(s): Once-monthly fitusiran prophylaxis significantly reduced bleeding versus factor/BPA prophylaxis with a median ABR of zero in PwHA/B with and without inhibitors, resulting in a meaningful improvement in HRQoL. Reported AEs were generally consistent with previously identified risks of fitusiran.
To cite this abstract in AMA style:
Kenet G, Nolan B, Zulfikar B, Antmen B, Kampmann P, Matsushita T, You C, Vilchevska K, Bagot C, Sharif A, Peyvandi F, Young G, Negrier C, Quan T, Poloskey S, Sussebach C, Shammas F, Andersson S, Mei B, Kavakli K. A Phase 3 study (ATLAS-PPX) to evaluate efficacy and safety of fitusiran, an siRNA therapeutic, in people with haemophilia A or B who have switched from prior factor or bypassing agent prophylaxis [abstract]. https://abstracts.isth.org/abstract/a-phase-3-study-atlas-ppx-to-evaluate-efficacy-and-safety-of-fitusiran-an-sirna-therapeutic-in-people-with-haemophilia-a-or-b-who-have-switched-from-prior-factor-or-bypassing-agent-prophylaxis/. Accessed March 22, 2024.« Back to ISTH 2022 Congress
ISTH Congress Abstracts - https://abstracts.isth.org/abstract/a-phase-3-study-atlas-ppx-to-evaluate-efficacy-and-safety-of-fitusiran-an-sirna-therapeutic-in-people-with-haemophilia-a-or-b-who-have-switched-from-prior-factor-or-bypassing-agent-prophylaxis/