Emicizumab represents a therapeutic innovation not only for haemophiliacs A with inhibitor but also for those without inhibitor. This is what the recently published Haven 3 study has shown. Thephase 3 study was performed on 152 enrolled patients aged ≥ 12 years and randomly assigned witha 2: 2: 1 ratio in 4 groups in order to evaluate prophylaxis with emicizumab. The first 3 groups included patients who had received episodic treatments (“on demand”) with factor VIII:
Group A. Patients were given subcutaneously (s.c.) emicizumab at the dose of 1.5 mg/kg of b.w. once a week.
Group B. Patients received emicizumab s.c. at the dose of 3 mg/kg of b.w. every 2 weeks.
Group C. Patients did not perform prophylaxis with emicizmab.
The primary end point was to evaluate the difference in the rate of bleeding/year (“Annualized Bleeding Rate”- ABR) of group A vs group B and group B vs group C.
Group D. To this group belonged patients who had received previously prophylaxis with factor VIII . They were given emicizumab s.c. at the maintenance dose of 1.5 mg / kg of b.w. once a week. Intra-individual comparisons were performed with patients who previously participated to the prospective non-interventional study (NIS) with the emicizumab.
In summary, the data show that ABR had 1.5 events in group A (95% confidence interval [CI], 0.9 – 2.5); 1.3 events in group B (95% CI, 0.8 – 2.3); 38.2 events in group C (95% CI, 22.9 – 63.8), with a rate of 96% for group A and 97% for group B respectively (P <0.001 for both comparisons) (Fig.1).
A total of 56% of participants in group A and 60% of those in group B respectively had no treated bleeding when compared to patients in group C where all had treated bleeding.
In the intra-individual comparison of 48 participants, prophylaxis with emicizumab resulted in a 68% lower ABR than in patients previously treated with factor VIII prophylaxis (P <0.001) (Fig. 2). No adverse events, excluding slight reactions at the injection site, neither episodes of thrombosis or thrombotic microangiopathy, nor development of anti-emicizumab antibodies or against factor VIII were observed.
In haemophiliacs A without inhibitor, subcutaneous administration of emicizumab once weekly or every 2 weeks has shown lower ABR than in hemophiliacs who did not use prophylaxis.
In addition, more than half of participants did not present treated bleeding. In the intra-individual comparison, treatment with emicizumab resulted in a significant reduction of ABR compared to prophylaxis with factor VIII, that is the standard treatment of hemophiliacs without inhibitor.
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J. Mahlangu, J. Oldenburg, I. Paz‐Priel, C. Negrier, M. Niggli, M.E. Mancuso, C. Schmitt, V. Jimenez‐Yuste, C. Kempton,C. Dhalluin, M.U. Callaghan, W. Bujan, M. Shima, J.I. Adamkewicz, E. Asikanius, G.G. Levy, and R. Kruse‐Jarres. N Engl J Med 2018;379:811-22.
Oldenburg J, Mahlangu JN, Kim B, et al. Emicizumab prophylaxis in hemophilia A with inhibitors. N Engl J Med 2017; 377: 809-18.
Shima M, Hanabusa H, Taki M, et al. Factor VIII–mimetic function of humanized bispecific antibody in hemophilia A. N Engl J Med 2016; 374: 2044-53.