The US Food and Drug Administration (FDA) has granted priority review for emicizumab (Hemlibra®) for adults and children with hemophilia A without factor VIII inhibitors.
Earlier this year, the agency awarded emicizumab breakthrough therapy designation for the same population.
Emicizumab is a bispecific factor IXa- and factor X-directed antibody approved by the FDA for routine prophylaxis to prevent or reduce the frequency of bleeding episodes in adults and children who have hemophilia A with factor VIII inhibitors.
The FDA based its decision to grant emicizumab priority review on the phase 3 HAVEN 3 study, results of which were presented recently at the World Federation of Hemophilia congress.
In HAVEN 3, emicizumab demonstrated a 68% reduction (P<0.0001) in treated bleeds based on an intra-patient comparison in patients who were previously enrolled in a prospective non-interventional study.
According to Genentech, co-developer of the drug, this makes emicizumab the first medicine to show superior efficacy to prior treatment with factor VIII prophylaxis, the current standard of care for people with hemophilia A without factor VIII inhibitors.
About HAVEN 3
The randomized, multicenter, open-label trial evaluated prophylaxis versus no prophylaxis in patients without factor VIII inhibitors.
The study included 152 patients 12 years or older who were previously treated with factor VIII therapy on-demand or as prophylaxis.
Patients previously treated with on-demand factor VIII were randomized in a 2:2:1 fashion to 1 of 3 treatment groups:
- Arm A received emicizumab prophylaxis at 3 mg/kg/wk for 4 weeks, followed by 1.5 mg/kg/wk until the end of study.
- Arm B received emicizumab prophylaxis at 3 mg/kg/wk for 4 weeks, followed by 3 mg/kg/2wks for at least 24 weeks.
- Arm C received no prophylaxis
Patients previously treated prophylactically with factor VIII were enrolled in Arm D and received emicizumab prophylaxis at 3 mg/kg/wk for 4 weeks, followed by 1.5 mg/kg/wk until the end of study.
The protocol permitted episodic treatment of breakthrough bleeds with factor VIII therapy.
Patients in the prophylaxis groups achieved a 96% (P<0.0001) and 97% (P<0.0001) reduction in treated bleeds, respectively, compared to those who received no prophylaxis.
Additionally, 55.6% of patients treated weekly and 60% treated every 2 weeks had no treated bleeds. In contrast, 0% in the prophylaxis group achieved zero treated bleeds.
Investigators observed no unexpected or serious adverse events (AEs), no thrombotic events, and no cases of thrombotic microangiopathy.
The most common AEs occurring in 5% or more of patients were injection site reactions, arthralgia, nasopharyngitis, headache, upper respiratory tract infection, and influenza.
The FDA is expected to make a decision regarding approval by October 4.