Once-monthly prophylaxis with the investigational small interference RNA therapeutic fitusiran was associated with a significant reduction in bleeding events when compared with clotting factor concentrate (CFC)/bypassing agent (BPA) prophylaxis in patients with hemophilia A and B with and without inhibitors. Guy Young, MD, of Children’s Hospital Los Angeles and University of Southern California Keck School of Medicine, presented the findings from the phase III ATLAS-PPX trial at the European Hematology Association (EHA) 2023 Congress on June 10.
Treatments that are better able to prevent bleeding and long-term joint disease are needed for hemophilia A and B, Dr. Young stated. Furthermore, there is a need to develop therapies that significantly reduce treatment burden for patients with hemophilia. “Historically, hemophilia was always treated with replacement of factor therapies, which were intravenous,” Dr. Young explained. “So, everybody had to be receiving intravenous therapy repeatedly.”
Although subcutaneous emicizumab is available for hemophilia A, there is still a need for a subcutaneously administered drug for hemophilia B that will lower the treatment burden for this population, Dr. Young noted.
“The thing that distinguishes fitusiran from any drug that’s currently available is that it can treat all types of hemophilia, hemophilia A and hemophilia B,” Dr. Young stated. “Having one drug that can be effective at preventing bleeding and is given subcutaneously and not frequently shows a lot of promise.”
The phase III ATLAS-PPX trial enrolled male patients 12 years of age and older with hemophilia A or B, with or without inhibitors, who had previously received CFC/BPA prophylaxis. Enrolled participants continued to use CFC/BPA prophylaxis for approximately six months prior to switching to once-monthly subcutaneous fitusiran prophylaxis 80 mg for seven months.
The investigators evaluated the annualized bleeding rate (ABR) in the CFC/BPA prophylaxis period and the fitusiran efficacy period, the latter of which began at study day 29 and continued to day 190. Spontaneous ABR (AsBR), joint ABR (AjBR), and health-related quality of life (HRQoL) were secondary endpoints.
In the 65 patients eligible for ABR analyses, 50 had hemophilia A and 15 had hemophilia B. The median ABRs were 4.4 with CFC/BPA and 0 with fitusiran prophylaxis. Approximately 63% of patients experienced no bleeds with fitusiran prophylaxis.
Compared with CFC/BPA prophylaxis, treatment with fitusiran was associated with significant reductions in the estimated ABR (p=0.0008), AsBR (p=0.0129), and AjBR (p=0.0242). Additionally, fitusiran improved HRQoL when compared with CFC/BPA as assessed by the Haem-A-QOL total score (least squares mean difference = -4.6; 95% CI -7.6 to -1.5; p<0.01).
Approximately 7.7% of patients who received CFC/BPA and 13.4% of patients treated with fitusiran prophylaxis experienced serious adverse events. During the fitusiran prophylaxis period, 25.4% of patients experienced elevations in alanine aminotransferase or aspartate transaminase that were more than three times the upper limit of normal. Two participants treated with fitusiran experienced suspected or confirmed thromboembolic events.
Any conflicts of interest declared by the authors can be found in the original abstract.
Reference
Kenet G, Nolan B, Zulfikar B, et al. A phase 3 study (ATLAS-PPX) to evaluate efficacy and safety of fitusiran in people with haemophilia A or B who have switched from prior clotting factor concentrate or bypassing agent prophylaxis. Abstract S303. Presented at the European Hematology Association (EHA) 2023 Congress; June 10, 2023; Frankfurt, Germany.