In a letter to the European Haemophilia Consortium, Roche has confirmed that one patient died in a phase 3 study of the bispecific antibody emicizumab. The death was considered to be unrelated to emicizumab, but, with the event following similar serious adverse reactions (SAEs) with other agents, it has added to questions about the safety of the experimental treatment.
Roche stated that it had received two reports of SAEs in a patient who was enrolled in the company’s HAVEN 1 trial. The patient experienced a serious rectal hemorrhage (the first reported SAE) and received bypassing agents, including repeated doses of activated prothrombin complex (aPCC), after which the patient developed signs of thrombotic microangiopathy (TMA) (the second SAE). Treatment of the hemorrhage was complicated because the patient declined blood transfusions. The patient subsequently died.
A preliminary assessment indicated that the clinical and laboratory characteristics of this case of TMA were consistent with what was observed in two previously reported cases involving Novo Nordisk’s NovoSeven (coagulation factor VIIa [recombinant]) and Shire’s Feiba (anti-inhibitor coagulant complex).
Participants in the phase 3 study were previously treated with episodic or prophylactic bypassing agents. The study protocol recommended avoiding the use of aPCC whenever possible and administering only approved bypassing agents at low doses.