Updated: Dec 12, 2019
On November 7, 2019, the New England Journal of Medicine published a letter to the Editor from Louis M. Aledort, M.D. from the Icahn School of Medicine at Mount Sinai. See below for his letter expressing concern over Hemlibra fatalities.
Emicizumab was recently licensed for the prophylactic treatment of hemophilia A in patients in whom antibodies (inhibitors) have not developed against the product they were using to treat or prevent bleeding episodes. Since the licensing of emicizumab in such patients, deaths have been reported in 2 patients without inhibitors who had factor VIII deficiency.1 The circumstances surrounding these deaths have not been made clear. Thus, 13 deaths (including in 11 patients with inhibitors) have now been reported since the original clinical trial was performed.2 In addition to deaths, thrombotic events and episodes of thrombotic microangiopathic hemolytic anemia have been noted in such patients. Neither of these complications has been reported in patients who had factor VIII deficiency without inhibitors and who were receiving emicizumab. In addition, the subcutaneous administration of emicizumab in newborns has been approved without any data to support its use.3 Such use in newborns is a welcome addition to therapy, but it is too early to know outcomes.
During prophylaxis with emicizumab, patients without inhibitors have had elevations in thrombin generation above their baseline level. It is unclear what role, if any, this finding plays in subsequent thrombotic events; also not known is the pathophysiological effect of microangiopathy in patients with inhibitors.
It is understandable that both patients with hemophilia A and their physicians are enthusiastic about the potential advantages of subcutaneous administration of emicizumab.4 However, I am concerned that we may be seeing the beginning of a serious public health issue. This population of patients has already been exposed to risks associated with therapy, and we should embrace this very important biologic agent with caution. More information is needed about adverse events associated with the use of emicizumab.
Louis M. Aledort, M.D. Icahn School of Medicine at Mount Sinai, New York, NY
Please note that the recorded number of fatalities is now up to 17.