Prophylaxis fitusiran may improve QoL and decrease bleeding in hemophilia patients: ATLAS-INH trial

Delhi: The effectiveness of fitusiran 80 mg monthly subcutaneous prophylaxis in persons with hemophilia A or B with inhibitors was proven in Phase 3 research. Fitusiran, in particular, considerably decreased bleeding, with a median ABR of zero and a considerable number of participants having no bleeds, leading to a meaningful improvement in health-related quality of life. The findings of this study were presented in the AMERICAN SOCIETY OF HEMATOLOGY annual meeting held on 12th December 2021.

Hemophilia A and B are uncommon bleeding diseases defined by poor clot formation caused by reduced thrombin production due to FVIII or FIX deficiency, respectively. Fitusiran is an experimental siRNA therapy delivered subcutaneously (SC) to restore thrombin production and rebalance hemostasis in persons with hemophilia A or B, with or without inhibitors.

Researchers demonstrate the safety and efficacy of fitusiran prophylaxis for PwHI in a phase 3 trial in this paper. The ATLAS-INH project is a randomized, open-label Phase 3 trial aimed to assess the effectiveness and safety of fitusiran in people with HIV. Eligible boys aged 12 years who were undergoing on-demand bypassing agent (BPA) therapy were randomly assigned in a 2:1 ratio to receive once-monthly 80 mg SC fitusiran prophylaxis or continue with on-demand BPA. In the effectiveness phase, the primary endpoint is the annualized bleeding rate (ABR) in PwHI on fitusiran prophylaxis versus those on BPA on-demand. Secondary objectives include spontaneous ABR, joint ABR, and Haem-A-QoL-measured quality of life (QoL).

The findings were as follow:

1. The research included 57 people who were chosen at random. At screening, the mean (range) age of the study participants was 28.4 (13-63) years.

2. Fitusiran vs on-demand BPA arm showed statistical significance for all primary and secondary objectives, with a substantial reduction in ABRs of treated bleeds: all, spontaneous, and joint bleeds. In the fitusiran arm, 25 patients (65.8%) had no treated bleeding episodes.

3. Fitusiran prophylactic medication was shown to be effective in individuals with hemophilia A and hemophilia B who had inhibitors.

4. Improvement in physical health domain score, with a difference of -28.72, as well as total HRQoL and between fitusiran and on-demand BPA arms, also attained statistical significance.

5. In total, 38 patients (92.7%) in the fitusiran arm and 11 patients (57.9%) in the on-demand BPA arm encountered at least one treatment-emergent adverse event (TEAE).

6. There were 13 treatment-emergent severe adverse events (TESAEs) recorded in 7 patients (17.1%) in the fitusiran arm and 8 TESAEs reported in 5 patients (26.3%) in the on-demand BPA arm.

7. In the fitusiran prophylaxis arm, TESAEs included device-related infection, hematuria, spinal vascular dysfunction, subclavian vein thrombosis, thrombosis, acute cholecystitis, chronic cholecystitis, and asymptomatic COVID-19.

8. One patient (2.4%) in the fitusiran arm suffered TEAEs that necessitated the cessation of the study medication (spinal vascular disorder and thrombosis). There were no TEAEs that were deadly.

In conclusion, reported TESAEs were largely consistent with what would be expected in an adult and adolescent population with severe hemophilia A or B treated with inhibitors, or with fitusiran's previously reported hazards. In ongoing clinical trials, a new fitusiran dosage regimen with a lower dose and frequency of administration is being investigated.

Reference:

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)" ASH 2021; Abstract 4.