Title: Emicizumab Prophylaxis in Hemophilia A with Inhibitors

Oldenburg, J et al.

 

What You Need to Know:

For patients with hemophilia A with factor VIII inhibitors, prophylaxis with emicizumab, a monoclonal antibody that restores the function of activated factor VIII, was effective in decreasing the rate of bleeding events compared to no prophylaxis.

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Trial Design:

  • Open label, multicenter, phase 3 study evaluated emicizumab prophylaxis in ≥12 year old patients with hemophilia A with factor VIII inhibitors that were receiving bypassing agents as episodic or prophylactic treatment
  • 109 male patients were randomly assigned (2:1) to receive emicizumab administered subcutaneously once weekly (group A; n=35) or no prophylaxis (group B; n=18)
  • Group C: patients who received prophylactic treatment with bypassing agents previously; also received emicizumab prophylaxis (n=49)
  • Group D: patients unable to enroll in groups A, B, or C before enrollment ended; also received emicizumab prophylaxis (n=7)
  • Primary endpoint: bleeding rate difference between groups A and B
  • Prospective, non-interventional study was also conducted to “enable direct and accurate intraindividual comparisons of previous outcomes with bypassing agents with outcomes with emicizumab prophylaxis”

Key Outcomes:

  • Annualized bleeding rate: 2.9 events for group A patients (95% CI: 1.7, 5.0) vs 23.3 events group B patients (95 CI: 12.3, 43.9) (87% difference favoring emicizumab prophylaxis; P<0.001)
  • 63% of group A patients (22/35) experienced no bleeding events vs 6% of group B patients (1/18)
  • “Among 24 participants in group C who had participated in a noninterventional study, emicizumab prophylaxis resulted in a bleeding rate that was significantly lower by 79% than the rate with previous bypassing-agent prophylaxis (P<0.001)”
  • Adverse events: 198 events reported by 103 patients receiving emicizumab prophylaxis; most common events reported were injection-site reactions (experienced by 15% of patients)
  • Four patients who “had received multiple infusions of activated prothrombin complex concentrate for breakthrough bleeding” reported thrombotic microangiopathy (n=2) and thrombosis (n=2)
  • Antidrug antibodies: not detected