Fitusiran prophylaxis leads to 61% reduction in bleeds among people with hemophilia A or B
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Key takeaways:
- Patients who received prophylactic fitusiran had significantly fewer bleeding episodes than those on prior prophylaxis.
- Almost two-thirds (63.1%) had no treated bleeds while receiving prophylactic fitusiran.
- Fitusiran demonstrated “statistically significant improvement in health-related quality-of-life measures.”
Once-monthly prophylactic fitusiran resulted in significantly fewer bleeding episodes compared with episodic-based on-demand treatment among males with hemophilia A or B with or without inhibitors, according to results of a phase 3 study.
Use of fitusiran (Sanofi) also led to significantly improved health-related quality-of-life scores, findings presented at International Society on Thrombosis and Haemostasis 2022 Congress showed.
Background
Prophylaxis is the standard-of-care treatment for patients with hemophilia, according to Gili Kenet, MD, director of Israel National Hemophilia Center at Sheba Medical Center and head of Amalia Biron Thrombosis Research Institute of Tel Aviv University.
Historically, the aim of prophylaxis has been to replace the missing clotting factor that corresponded with the type of disease with the intent of preventing bleeding.
“Now the bar is rising because the regular administration of hemostatic agents has the goal of preventing bleeding in patients with hemophilia while allowing them to lead active lives and achieve quality of life that is comparable with patients who do not have hemophilia,” Kenet said during a presentation.
Fitusiran — a subcutaneous small-interference RNA therapy — has “raised the expectations” of what is possible for the treatment of hemophilia A and B, she said. Prophylactic use of the investigational treatment has shown the ability to significantly reduce annualized bleeding rates compared with on-demand treatment options in previous phase 3 studies, she added.
“Fitusiran targets antithrombin to restore specific thrombi generation and rebalance hemostasis without actually replacing the missing population factors,” Kenet said.
Methodology
The multicenter phase 3 ATLAS-PPX trial enrolled 80 males aged 12 years or older with hemophilia A or B, with (n = 30) or without (n = 50) inhibitors, who had received previous treatment with prophylactic factor or bypassing agents.
Kenet and colleagues divided the study into an initial standard-of-care period, when patients continued receiving prophylactic factor or bypassing agents for 6 months, and a treatment period, when patients began taking prophylactic once-monthly subcutaneous fitusiran dosed at 80 mg starting at month 7.
Annualized bleeding rate during the standard-of-care and treatment periods served as the study’s primary endpoint. Secondary endpoints included spontaneous annualized bleeding rate, annualized bleeding rate in joints, health-related quality of life and safety.
Key findings
Sixty-five patients remained eligible for primary endpoint analysis of annualized bleeding rate, including 50 patients with hemophilia A and 15 with hemophilia B. Investigators divided the study into two cohorts — 19 patients with inhibitors (mean age, 27.8 ± 17.1 years) and 46 patients without inhibitors (mean age, 23.5 ± 7.3 years).
Researchers reported a median annualized bleeding rate of 0 (95% CI, 0-2.3) among patients who received fitusiran prophylaxis compared with 4.4 (95% CI, 2.2-10.9) for those who received prophylactic factor or bypassing agents. This equaled a statically significant 61.1% reduction in annualized bleeding rate for patients who received fitusiran (P -= .0008).
Additionally, 41 patients (63.1%) had no treated bleeds while receiving prophylactic fitusiran during the treatment period.
Investigators noted that spontaneous annualized bleeding rate, annualized bleeding rate in joints and health related quality-of-life assessments all showed significant improvement during the treatment period with fitusiran. This included median spontaneous and joint bleeding rates of zero during the treatment period compared with 2.2 for both values during the standard-of-care period.
Safety analysis showed 71.6% of patients had a treatment-related adverse event during the fitusiran treatment period, compared with 33.8% in the standard-of-care period. Serious treatment-related adverse events occurred among 13.4% of patients during the fitusiran treatment period, including two patients who discontinued the therapy.
No treatment-related deaths occurred during either the standard-of-care or fitusiran treatment periods.
Clinical implications
Fitusiran prophylaxis resulted in statistically significant reductions in bleeding events vs. standard-of-care treatment among patients with hemophilia A or B, regardless of whether they developed inhibitors, Kenet noted.
“[This] resulted in statistically significant improvement in health-related quality-of-life measures,” she said. “Reported adverse events were generally consistent with previously identified risks of fitusiran or what is anticipated in an adult and adolescent population of patients with severe hemophilia A or B, with or without inhibitors.”
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Kenet G, et al. Abstract LB 01.1 Presented at: International Society on Thrombosis and Haemostasis 2022 Congress; July 9-13, 2022; London.
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