Treating Hemophilia A
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Hemophilia A is an inherited bleeding disorder
caused by a deficiency in factor VIII activity. The current standard of care includes prophylactic
intravenous factor VIII infusions. However, these infusions can result in the
development of anti-factor VIII antibodies that can inhibit efficacy and increase morbidity. Intravenous bypassing agents such as activated
factor VII and activated prothrombin complex may be required to counteract these effects. Emicizumab is a recombinant humanized bispecific
monoclonal antibody that binds to activated factor IX and factor X, brings them into
proximity, and restores the scaffolding function of the missing activated factor VIII. In the phase 3, international, open label
HAVEN study, investigators randomized in a 2:1 ratio 53 participants with hemophilia
A of any severity, with documented high factor VIII inhibitor levels and episodic treatment
with bypassing agents, to receive weekly subcutaneous emicizumab prophylaxis or no prophylaxis. An additional 56 participants who had a history
of prophylactic use of bypassing agents or who were not able to enroll into other study
groups were assigned to treatment with emicizumab. The primary endpoint was the reduction in
annualized bleeding rates after 24 weeks of treatment. Emicizumab prophylaxis resulted in a statistically
significant decrease in annualized bleeding rate: 2.9, as compared with 23.3 in the no
prophylaxis group, which represented a decrease of 87%. In addition, 63% of the participants randomized
to emicizumab prophylaxis had no bleeding. Thrombotic microangiopathy and thrombosis
were serious adverse events reported in 4 participants receiving both emicizumab and
activated prothrombin complex concentrate, but these effects resolved after cessation
of the bypassing agent. The authors conclude that emicizumab prophylaxis
prevented or substantially reduced episodes of bleeding in patients with hemophilia A with inhibitors. Full trial results are available at NEJM.org.

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