Fitusiran prophylaxis safe, effective for patients with hemophilia A or B with inhibitors
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A once-monthly subcutaneous prophylaxis dose of fitusiran appeared safe and effective for people with hemophilia A or B with inhibitors, according to results of a randomized phase 3 study presented at ASH Annual Meeting and Exposition.
Fitusiran (ALN-AT3, Alnylam Pharmaceuticals), an investigational small interfering RNA therapeutic that targets antithrombin, significantly reduced bleeding and led to meaningful improvement in health-related quality of life for this patient population, the data showed.
“Fitusiran can improve the quality of life for patients with hemophilia A and B in a number of ways,” Guy Young, MD, director of the hemostasis and thrombosis program at Children's Hospital Los Angeles and professor of pediatrics at Keck School of Medicine of University of Southern California, told Healio. “First, it was shown to be exceptionally effective at preventing bleeding. When compared with the group of patients who did not receive prophylaxis, it reduced the bleeding by over 90%. Second, it substantially reduces the burden of treatment by offering a once-per-month subcutaneous injection in place of what would otherwise be many IV infusions per month to treat or try to prevent bleeding events.”
The open-label ATLAS-INH study evaluated the safety and efficacy of fitusiran among 57 boys and men aged 12 years or older (mean age at screening, 28.4 years; range, 13-63) with hemophilia A or B with inhibitors. Researchers randomly assigned participants in a 2:1 ratio to 80 mg subcutaneous, once-monthly fitusiran prophylaxis or to continue on-demand treatment with bypassing agents (BPA). More patients had hemophilia A vs. hemophilia B in both the fitusrian (n = 29 vs. 9) and BPA (n = 16 vs. 3) groups.
Annualized bleeding rate (ABR) among those on fitusiran prophylaxis vs. BPAs on demand during the efficacy period served as the primary endpoint. Secondary endpoints included spontaneous ABR, joint ABR and quality of life.
Results showed fitusiran conferred a significant reduction in estimated ABRs of all treated bleeds (1.67 vs. 18.07; rate ratio = 0.09; 95% CI, 0.04-0.19), treated spontaneous bleeds (0.87 vs. 15.68; rate ratio = 0.06; 95% CI, 0.03-0.12) and treated joint bleeds (1.35 vs. 13.76; rate ratio = 0.1; 95% CI, 0.05-0.21; P < .0001 for all) compared with BPA on demand.
About two-thirds of patients in the fitusiran group (65.8%) had zero treated bleeding events. Median observed ABR for all treated, spontaneous and joint bleeds was zero with fitusiran vs. 16.8 (95% CI, 6.7-23.5), 13.4 (95% CI, 3.4-21.8) and 11.7 (95% CI, 3.4-16.8) with BPA on demand.
Fitusiran prophylaxis treatment showed efficacy among both patients with hemophilia A and hemophilia B with inhibitors. Researchers also reported statistically significant improvement with fitusiran in physical health domain score, with a difference of 28.72 (95% CI, 39.07 to 18.37), as well as in overall health-related quality of life.
A larger proportion of patients in the fitusiran vs. on-demand BPA group (92.7% vs. 57.9%) experienced at least one treatment-emergent adverse event. Thirteen serious treatment-emergent adverse events — including device related infection, hematuria, spinal vascular disorder, subclavian vein thrombosis, thrombosis, acute cholecystitis, chronic cholecystitis and asymptomatic COVID-19 — occurred among seven patients in the fitusiran group. Eight serious treatment-emergent adverse events occurred among five patients in the on-demand BPA group.
One patient in the fitusiran group experienced spinal vascular disorder and thrombosis that led to study drug discontinuation. No fatal treatment-emergent adverse events occurred.
When asked about the next steps for research, Young noted that results of a sister study with a similar design among people with hemophilia A and hemophilia B without inhibitors was scheduled for presentation at ASH during the late-breaking abstract session.
“Second, additional studies are under way to further improve upon the safety of this agent,” Young said. “Third, a pediatric study is also under way aiming to ensure that children can also benefit from this drug.”
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Young G, et al. Abstract 4. Presented at: ASH Annual Meeting and Exposition. Dec. 11-14, 2021; Atlanta.
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