Despite the fact that many rare diseases featured on Rare Disease Advisor lack a definite cure, it is important to take a wide view regarding the advancements in rare disease therapeutics in their proper historical context; by multiple measures, we are living in the most exciting, innovative period of drug development. Many first-line medications for certain conditions have been around for only a few years, and there is every indication that we are entering into a golden age of experimentation, competition, and crucially, results. 

One such innovative drug is emicizumab, used in treating hemophilia A. It is a bispecific humanized monoclonal antibody that is administered subcutaneously. It essentially works by bridging activated factor IX (FIX) and factor X (FX) to substitute for the missing activated factor VIII (FVIII), thus improving hemostasis. 

Studies indicate that emicizumab can successfully prevent bleeds in patients with hemophilia A, including in patients who have developed FVIII inhibitors, when administered once every 2 to 4 weeks. Clinical trials have time and again proven the efficacy of emicizumab in achieving various important bleeding outcomes, such as reducing annualized bleeding rates. In up to 90% of individuals with hemophilia A, emicizumab recipients have ceased to report any bleeding episodes requiring treatment. 

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This is astounding progress in a disease category that used to strike fear among European royalty for centuries, as it was an insidious condition capable of the premature killing of male heirs.  

Read more about hemophilia etiology 

Emicizumab: A General Consensus

In Blood, Callaghan and colleagues conducted a study to assess the long-term safety and efficacy of emicizumab in patients with hemophilia A. They used pooled data from the long-term follow-up of HAVEN 1-4, a series of studies assessing the pharmacokinetics of emicizumab. 

The endpoints of the study were all related to bleeding—spontaneous bleeds, joint bleeds, and treatable bleeds, among others. In addition, the study had an emphasis on reported adverse events. The efficacy of the drug was monitored until study withdrawal or the end of the clinical study period. 

“In the primary analyses of the HAVEN studies, emicizumab prophylaxis resulted in statistically significant and clinically meaningful reductions in annualized bleeding rates across bleed-related endpoints, regardless of age, FVIII inhibitor status, or dosing regimen,” the authors reported. 

A more detailed analysis of the data indicates that the administration of emicizumab once every 4 weeks “provided sustained clinically meaningful bleed prevention”: in colloquial terms, this means that emicizumab works remarkably well and gives patients the best shot at a normal life. In terms of its safety profile, despite reports of adverse events, it has been shown to be safe and well-tolerated on a long-term basis. 

“Emicizumab prophylaxis an efficacious and well-tolerated option for improving the care of patients with hemophilia A,” Callaghan et al wrote. 

Latest Expert Opinion on Emicizumab 

In Hematology, an expert opinion paper published in January 2023 provides us with a fresh look at the merits of emicizumab in the treatment of patients with hemophilia A. 

This expert opinion takes a balanced approach in assessing the use of emicizumab in hemophilia A; it acknowledges many of its advantages, but at the same time highlights areas of concern. 

Although emicizumab has undoubtedly shifted the treatment landscape of hemophilia A for the better, it remains true that prophylaxis is the gold standard for treating patients with severe hemophilia. Prophylaxis is one of the oldest and most well-researched forms of therapy, based on the concept of substituting missing coagulation factors. The main pitfalls of prophylaxis therapy is the need for continuous venous access for intravenous administration, the threat of the development of neutralizing antibodies against FVIII, and the relatively high cost of treatment.

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This expert opinion acknowledges the current body of evidence that points to emicizumab as a safe and effective form of treatment; it reduces annualized bleeding rates, and a significant percentage of users report zero bleeds. However, there are questions about how to manage patients in a perioperative setting. Some scientists believe that the addition of FVIII prophylaxis provides the best protection against postoperative bleeding. 

The authors also highlight concerns about the use of emicizumab in previously untreated neonates with hemophilia A. This is relevant because many individuals are diagnosed with hemophilia A in the neonatal stage. The consensus at present is that prophylaxis should be started early, with emicizumab being a potentially important drug that helps reduce the risk of hemorrhage. Nevertheless, the medical literature regarding emicizumab use in neonates is limited, although current results are promising. 

Another question that the experts in this study grapple with is the usefulness of the laboratory monitoring of emicizumab-treated patients. Current evidence does not indicate a need for the therapeutic monitoring of this drug; however, some scientists advocate for the use of bovine chromogenic assay and modified activated partial thromboplastin time as methods for monitoring emicizumab therapy. 

“Emicizumab has been shown to be a promising therapeutic option for hemophilia A,” the expert opinion concluded. “Still, more studies are needed to help confirm these findings and address some of the concerns that continue to plague clinicians and are outlined in this article.” 


Callaghan MU, Negrier C, Paz-Priel I, et al. Long-term outcomes with emicizumab prophylaxis for hemophilia A with or without FVIII inhibitors from the HAVEN 1-4 studiesBlood. 2021;137(16):2231-2242. doi:10.1182/blood.2020009217

López-Jaime FJ, Benítez O, Díaz Jordán BL, et al. Expert opinion paper on the treatment of hemophilia A with emicizumabHematology. 2023;28(1):2166334. doi:10.1080/16078454.2023.2166334