Fitusiran prophylaxis was associated with a significantly lower annualized bleeding rate for treated bleeds, compared with on-demand clotting factor concentrate use, in a study of patients with severe hemophilia A or B without inhibitors. Study results were reported in the journal Lancet Haematology.
“To our knowledge, fitusiran prophylaxis is the first therapy to show haemostatic efficacy in both haemophilia A or B, regardless of inhibitor status, and therefore has the potential to be transformative in the management of all people with haemophilia,” the study investigators wrote in their report.
The open-label, phase 3 ATLAS-A/B study (ClinicalTrials.gov Identifier: NCT03417245) included male patients 12 years of age or older who had severe hemophilia A or B without inhibitors, and who had a history of receiving on-demand therapy with clotting factor concentrates.
Participants in the study were stratified based on bleeding event history and hemophilia type and randomly assigned 2:1 to treatment groups. The treatment groups were assigned to either receive 80 mg subcutaneous fitusiran prophylaxis on a monthly basis or continue to use on-demand clotting factor concentrates for 9 months. The annualized bleeding rate of treated bleeds was the primary study endpoint.
There were 80 patients randomized to the fitusiran prophylaxis group and 40 patients randomized to the group receiving on-demand clotting factor concentrates. Mean patient ages were 33.9 years and 33.6 years, respectively. In each group, 78% of patients had hemophilia A. During the 6 months before screening, the median bleeding rates were 10 (interquartile range [IQR], 8.0-16.5) in the fitusiran prophylaxis group and 10 (IQR, 7.0-14.5) in the factor on-demand group.
Each treatment group had a median follow-up duration of 7.8 months. For the fitusiran group, the median observed annualized bleeding rate was 0.0 (IQR, 0.0-3.4), compared with 21.8 (IQR, 8.4-41.0) for the factor on-demand group, for any treated bleeding event in patients evaluated during the efficacy period.
Additionally, patients in the fitusiran group had a lower mean annualized bleeding rate than the factor on-demand group did (rate ratio, 0.101; 95% CI, 0.064-0.159; P <.0001). The mean annualized bleeding rates were 3.1 (95% CI, 2.3-4.3) for the fitusiran group and 31.0 (95% CI, 21.1-45.5) for the factor on-demand group. Additionally, there were no treated bleeds in 40 (51%) of 79 patients in the fitusiran group, compared with 2 (5%) of 40 patients in the factor on-demand group.
Treatment-emergent serious adverse events reportedly occurred in 5 (6%) patients evaluated in the fitusiran prophylaxis group and in 5 (13%) patients of the factor on-demand group. In the fitusiran group, the most common treatment-emergent adverse event overall was an increase in the alanine aminotransferase level, occurring in 18 (23%) patients. Treatment-related thrombosis or death reportedly did not occur in either study group.
“In conclusion, fitusiran prophylaxis provided sustained protection against bleeding that was associated with a meaningful improvement in quality of life in people with severe haemophilia A or B without inhibitors, and was well tolerated,” the study investigators stated in their report.
Disclosures: Some authors have declared affiliations with or received grant support from the pharmaceutical industry. Please refer to the original study for a full list of disclosures.
Srivastava A, Rangarajan S, Kavakli K, et al. Fitusiran prophylaxis in people with severe haemophilia A or haemophilia B without inhibitors (ATLAS-A/B): a multicentre, open-label, randomised, phase 3 trial. Lancet Haematol. Published online March 29, 2023. doi:10.1016/S2352-3026(23)00037-6.