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Fitusiran safe and effective in patients with haemophilia A and B with inhibitors

The phase III ATLAS-INH study demonstrated the efficacy of the 80 mg monthly subcutaneous prophylaxis dose of fitusiran in people with haemophilia A or B with inhibitors. Fitusiran significantly reduced bleeding with a median annualised bleeding rate of zero and a significant proportion of people with zero bleeds, resulting in a meaningful improvement in health-related quality of life.

Haemophilia A and B are X-linked, recessive rare bleeding disorders characterised by ineffective clot formation due to impaired thrombin generation as a result of deficiency of FVIII or FIX, respectively. Thus far, treatment has mainly relied on replacing the missing protein. However, about 30% of haemophilia A patients and 5% of haemophilia B patients develop neutralising anti-drug (anti-factor) antibodies and these patients have a dismal prognosis. Therefore, better agents are needed to prevent bleeding in inhibitor patients and reduce mortality, morbidity and improve quality of life. Fitusiran is a subcutaneously (SC) administered investigational siRNA therapeutic designed to lower the antithrombin, with the goal of promoting sufficient potential to generate thrombin to rebalance haemostasis in people with haemophilia A or B, with or without inhibitors. The ATLAS-INH study was designed to evaluate the efficacy and safety of fitusiran in people with haemophilia A or B, with inhibitors (PwHI).

ATLAS-INH Study design

The phase III ATLAS-INH study included male patients of at least twelve years old, with haemophilia A or B, who developed inhibitors while receiving on-demand treatment with bypassing agents (BPAs). Patients were randomised 2:1 to receive monthly 80 mg subcutaneous fitusiran prophylaxis (N= 38), with use of on-demand BPAs for treatment of breakthrough bleeds, or to continue with on-demand BPA (N= 19). Treatment was given for a period of nine months, after which the primary endpoint of annualised bleeding rate (ABR) in PwHI on fitusiran prophylaxis compared to those on BPA on-demand was assessed.


Patient demographics and characteristics at baseline were generally similar between the two study arms. Median age of study participants was 28.4 years and 21.1% of patients had haemophilia B. The mean number of bleeding episodes in the last six months prior to screening was 12.6, translating to an ABR of roughly 25. A statistically significant and clinically relevant reduction in median ABR was observed for fitusiran (median ABR of 0 vs. 16.8). The estimated mean ABR was 18.1 for patients receiving on-demand BPAs and 1.7 for patients treated with fitusiran. A total of 25 patients in the fitusiran arm (65.8%) had zero treated bleeding events. Furthermore, statistical significance was achieved for all secondary endpoints with a reduction in spontaneous bleeds (median ABR of 13.4 vs. 0.0) and joint bleeds (median ABR of 11.7 vs. 0.0) for fitusiran vs. the on-demand BPA arm. Importantly, the efficacy of fitusiran prophylaxis treatment was observed in both haemophilia A and haemophilia B patients with inhibitors. Statistical significance was also achieved for improvement in physical health domain score, with a difference of -28.72 as well as overall in health-related quality of life (HRQoL) (difference -14.85) between fitusiran and on-demand BPA arms (p< 0.0001).

Almost all patients (92.7%) in the fitusiran arm and 11 patients (57.9%) in the on-demand BPA arm experienced at least one treatment emergent adverse event (TEAE). In total, seven patients (17.1%) reported treatment emergent serious adverse events (TESAEs) in the fitusiran arm, as compared to five patients (26.3%) in the on-demand BPA arm. One patient in the fitusiran arm experienced TEAEs that resulted in study drug discontinuation (spinal vascular disorder and thrombosis). There were no fatal TEAEs reported. All 11 cases of elevated transaminases in the fitusiran population were of mild to moderate severity and did not lead to study drug discontinuation in any of these patients. One patient in the fitusiran arm discontinued the study due to a thrombotic event.


Once-monthly subcutaneous 80 mg fitusiran prophylaxis resulted in a significantly lower rate of bleeding events among people with haemophilia A or B with inhibitors, and improved HR-QoL. The reported TEAEs in the fitusiran prophylaxis arm were generally consistent with previously identified risks of fitusiran or what is anticipated in an adult and adolescent population with severe haemophilia A or B.


Young G, et al. Efficacy and Safety of Fitusiran Prophylaxis, an siRNA Therapeutic, in a Multicenter Phase 3 Study (ATLAS-INH) in People with Hemophilia A or B, with Inhibitors (PwHI). Presented at ASH 2021; Abstract 4.

Speaker Guy Young

Guy Young

Guy Young, MD, Children's Hospital Los Angeles, University of Southern California, United States


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