What is the role of emicizumab in the treatment of hemophilia A?

Updated: Jan 14, 2019
  • Author: Douglass A Drelich, MD; Chief Editor: Srikanth Nagalla, MBBS, MS, FACP  more...
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Answer

Emicizumab is a first-in-class bispecific monoclonal antibody that performs the function of activated FVIII, bridging activated FIX and FX to restore the coagulation cascade, but is unaffected by FVIII inhibitors. In November 2017, following a priority review, the FDA approved emicizumab for routine prophylaxis of bleeding episodes in adult and pediatric patients with hemophilia A who have FVIII inhibitors. Approval was based on the HAVEN 1 and 2 clinical trials.

The HAVEN 1 trial included 109 adult and adolescent males aged 12 years or older who had hemophilia A with inhibitors. Patients taking emicizumab experienced about 2.9 treated bleeding episodes per year, compared with about 23.3 treated bleeding episodes per year for patients who did not receive prophylactic treatment, representing an 87% reduction in the rate of treated bleeding episodes (p < 0.001). Emicizumab treated patients also reported an improvement in hemophilia-related symptoms (painful swellings and joint pain) and physical functioning (pain with movement and difficulty walking). [33]

Interim results from the single-arm HAVEN 2 study in children aged younger than 12 years with hemophilia A with inhibitors who received emicizumab prophylaxis are consistent with the positive results from the HAVEN 1 study. After a median observation time of 12 weeks, only 1 of the 19 study patients receiving emicizumab reported a treated bleed. [34]

Three patients in the HAVEN 1 trial who experienced breakthrough bleeding despite emicizumab prophylaxis and were treated with PCC developed thrombotic microangiopathy (TMA). Episodes of TMA occurred only in patients who received, on average, cumulative doses of PCC of more than 100 U/kg daily for 24 hours or more. This complication appears to represent a unique interaction between emicizumab and PCC, as no cases of TMA had previously been reported in patients receiving PCC alone. Strategies for treating breakthrough bleeding in patients receiving emicizumab may include the use of recombinant FVIIa, FVIII in patients with a low inhibitor titer, and lower doses of PCC. [35]


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