Fitusiran, a novel RNA interference (RNAi) therapeutic developed by Alnylam Pharmaceuticals and Sanofi, is emerging as a promising treatment for hemophilia A and B. Clinical data from phase 3 studies demonstrate its potential to significantly reduce annualized bleeding rates in patients, regardless of inhibitor status. This subcutaneous drug, administered monthly or bimonthly, targets antithrombin, offering a new prophylactic approach to hemophilia management.
Efficacy in Hemophilia A and B Without Inhibitors
The phase 3 ATLAS-A/B trial (NCT03417245) evaluated fitusiran's efficacy compared to on-demand treatment with factor concentrates in severe hemophilia A and B patients without inhibitors. The study, which included 120 patients aged 12 years or older, randomized participants to receive either fitusiran (n=80) or on-demand clotting factor concentrates (n=40). Results showed a mean annualized bleeding rate of 0.0 in the fitusiran group compared to 21.8 in the on-demand factor group. Notably, 51% of patients in the fitusiran group experienced no treated bleeds, compared to only 5% in the on-demand group. The median follow-up was 7.8 months for both groups. Increased alanine aminotransferase concentrations (23%) were the most common treatment-emergent adverse event in the fitusiran group.
Efficacy in Hemophilia A and B With Inhibitors
The ATLAS-INH study (NCT03417102) assessed fitusiran's efficacy in hemophilia A and B patients with inhibitors. The trial included 57 individuals, with 38 receiving fitusiran and 19 receiving on-demand treatment. The annualized bleeding rate was significantly lower in the fitusiran group, demonstrating an approximate reduction of 90.8%. Approximately 66% of individuals in the fitusiran group had 0 treated bleeds compared to 1 in the on-demand group. Similar to the other trial, the most frequent adverse event was increased alanine aminotransferase (32%) in the fitusiran group.
Mechanism of Action and Potential Benefits
Fitusiran's mechanism of action involves silencing the antithrombin gene using RNAi technology. This approach aims to rebalance hemostasis and reduce the frequency of bleeding episodes in hemophilia patients. RNAi therapies offer the potential for highly specific and personalized treatment approaches. While challenges remain, such as delivery methods and potential immune system activation, fitusiran represents a significant advancement in precision therapy for hemophilia.
Role of Pharmacists in Hemophilia Management
Pharmacists play a crucial role in managing hemophilia A and B, particularly in monitoring patients and spotting symptoms due to the unpredictability of bleeding. They can collaborate with other healthcare professionals to personalize treatment and provide expert advice on medication management.
