Emicizumab revolution in treating Hemophilia

Abstract

HemophiliaA (H.A.) has beenanuncommon hereditary X-linked bleeding disorder indicated by clotting factorVIII (FVIII)deficiency, leading to impaired hemostasis. H.A. affects approximately one in 5,000male births in the U.S., often resulting in spontaneous joint bleeding, chronic pain, and an increased risk of cerebral hemorrhage. Prophylactic treatment with FVIII replacement or the bispecific antibody emicizumab has become a crucial strategy to prevent bleeding episodes and long-term tissue damage. Emicizumab, approved by the FDA & EMA in2018, mimics FVIII activity by binding to activated factorIX (FIXa) & factorX (F.X.), facilitating blood clotting regardless of FVIII inhibitors. The development of emicizumab involved extensive bioengineering to optimize its safety, stability, and efficacy, leading to its successful application in clinical trials. These trials demonstrated that emicizumab significantly decreases the annualized bleeding rate in studied cases with or without inhibitors, including severe H.A. cases, with a favorable safety profile and minimal adverse events. Emicizumab's subcutaneous administration, high bioavailability, and predictable pharmacokinetics make it a practical option for H.A. prophylaxis. Despite its benefits, emicizumab can interfere with specific coagulation assays and may develop anti-drug antibodies (ADAs) in rare cases, potentially reducing its efficacy. Ongoing research and post-marketing surveillance continue to assess its long-term safety and effectiveness, making emicizumab a transformative treatment in managing hemophilia A.