“Approximately 70% of patients with haemophilia do not have access to factor replacement therapy,” said Dr Alok Srivastava (Christian Medical College Vellore, India). “In addition, this treatment needs to be administered intravenously, multiple times per week, placing a heavy treatment burden on our patients. New therapeutic options are needed to reduce bleeding and treatment burden, and increase the quality of life for patients with haemophilia.”
The ATLAS-A/B trial (NCT03417245) included 120 patients with severe haemophilia A or B without inhibitors. Patients were randomised 2:1 to receive fitusiran, a small interference RNA agent targeting antithrombin (80 mg, subcutaneous, once monthly), or on-demand factor concentrates. The primary endpoint was the ABR after 9 months. Median ABR was 0.0 in the fitusiran arm versus 21.8 in the on-demand arm (P<0.0001). For patients with haemophilia A or B treated with fitusiran, median ABRs were 0.0 and 2.7, respectively. In addition, 50.6% of the patients in the fitusiran arm did not display any treated bleedings during the study.
The Haemophilia Quality of Life Questionnaire for Adults (Haem-A-QoL) showed a reduction of 9.68 in total score, and 23.07 in physical health score for patients treated with fitusiran, representing a clinically meaningful improvement in quality of life. The safety analysis did not reveal unexpected safety issues. Treatment-emergent adverse events (AEs) were reported in 78.5% of the fitusiran receivers and in 45.0% of the patients in the on-demand arm.
The majority of treatment-emergent AEs were mild, moderate, and reversible. In the fitusiran arm, 6.3% of the patients experienced a serious treatment-emergent AE, compared with 12.5% of the patients in the on-demand arm. The most prevalent treatment-emergent AE of special interest was an increased level of alanine aminotransferase, which was reported in 15.2% of the fitusiran receivers. No thrombotic events were observed.
1. Srivastava A, et al. Fitusiran, an Investigational siRNA Therapeutic Targeting Antithrombin for the Treatment of Hemophilia: First Results from a Phase 3 Study to Evaluate Efficacy and Safety in People with Hemophilia A or B Without Inhibitors (ATLAS-A/B). LBA-3 ASH 2021 Scientific Sessions, 11-14 December.