Fitusiran in haemophilia: a breakthrough drug with many unknowns

Haemophilia A, defined by factor VIII (FVIII) deficiency, and haemophilia B, defined by factor IX (FIX) deficiency, are X chromosome linked diseases characterised by reduced thrombin generation and bleeding symptoms. 1 Peyvandi F Garagiola I Young G The past and future of haemophilia: diagnosis, treatments, and its complications. Lancet. 2016; 388: 187-197 Summary Full Text Full Text PDF PubMed Scopus (261) Google Scholar Prophylaxis with replacement FVIII and FIX is considered the gold standard in haemophilia treatment. Over the past two decades, the treatment landscape in haemophilia has changed substantially with the introduction of extended half-life products, FVIII-activity mimicking agents, and innovative drugs, which aim to rebalance the anticoagulant potential through the inhibition of natural anticoagulants. 2 Nogami K Shima M Current and future therapies for haemophilia beyond factor replacement therapies. Br J Haematol. 2023; 200: 23-34 Crossref PubMed Scopus (2) Google Scholar One of the rebalancing drugs, fitusiran, an investigational small interfering RNA agent, reduces antithrombin synthesis in the hepatocytes, ultimately rebalancing haemostasis. 3 Sehgal A Barros S Ivanciu L et al. An RNAi therapeutic targeting antithrombin to rebalance the coagulation system and promote hemostasis in hemophilia. Nat Med. 2015; 21: 492-497 Crossref PubMed Scopus (210) Google Scholar Efficacy and safety of fitusiran prophylaxis in people with haemophilia A or haemophilia B with inhibitors (ATLAS-INH): a multicentre, open-label, randomised phase 3 trialSubcutaneous fitusiran prophylaxis resulted in statistically significant reductions in annualised bleeding rate in participants with haemophilia A or haemophilia B with inhibitors, with two-thirds of participants having zero bleeds. Fitusiran prophylaxis might show haemostatic efficacy in participants with haemophilia A or haemophilia B with inhibitors; therefore, the therapeutic might have the potential to improve the management of people with haemophilia. Full-Text PDF