Efanesoctocog alfa: a new standard for haemophilia A prophylaxis?

The arrival of new subcutaneous products for prophylaxis in hemophilia has focused on preventing bleeding by normalizing thrombin generation. Emicizumab has been a paradigm shift, and while some experts prefer prophylaxis with coagulation factor VIII (CFVIII), others consider emicizumab as the reference treatment due to its efficacy and safety. CFVIII extended half-life concentrates have improved previous treatments, but their effectiveness has been limited by their half-life, restricted by von Willebrand factor. New products, such as efanesoctocog alfa, approved in 2023, offer an ultra-long half-life, reducing the treatment burden. This recombinant product presents modifications that extend its plasma half-life and improve thrombin generation. The clinical efficacy of weekly prophylaxis has been demonstrated in the XTEND-1 and XTEND-Kids studies, showing good results in efficacy and tolerance, with a low incidence of inhibitors. Indirect comparisons suggest that efanesoctocog alfa could be superior to emicizumab in bleeding prophylaxis in adults and adolescents without inhibitors. In conclusion, efanesoctocog alfa inaugurates a new class of ultra-long half-life CFVIII, offering a significant therapeutic opportunity for hemophilia by normalizing thrombin generation in a physiological manner. However, more studies are needed to evaluate its efficacy and safety in different clinical scenarios.