The following is a summary of “Phase 3 Trial of Concizumab in Hemophilia with Inhibitors,” published in the August 2023 issue of Hematology by Matsushita et al.
Researchers conducted a retrospective study to evaluate the efficacy and safety of concizumab in patients with hemophilia A or B with inhibitors, following the proof-of-concept results from the Explorer4 trial.
They initiated the Explorer7 trial to assess concizumab in individuals with hemophilia A or B who had inhibitors. Patients divided into group 1 received no prophylaxis (24 weeks), while group 2 had concizumab prophylaxis (32 weeks). Groups 3 and 4 received nonrandom concizumab prophylaxis (24 weeks). After temporarily halting concizumab therapy due to nonfatal thromboembolic events in three patients, including one from the explorer7 trial, treatment recommenced with a 1.0 mg/kg loading dose, followed by a daily 0.2 mg/kg dose (adjustable based on concizumab plasma concentration at week 4). The primary endpoint analysis compared treated bleeding episodes between groups 1 and 2 with safety and patient-reported outcomes assessments.
The results showed 133 patients; 19 were randomly assigned to group 1, 33 were to group 2, and 81 were in groups 3 and 4. In group 1, the estimated mean annualized bleeding rate was 11.8 episodes (95% CI, 7.0 to 19.9); in group 2, it was 1.7 episodes (95% CI, 1.0 to 2.9) (rate ratio, 0.14 [95% CI, 0.07 to 0.29]; P<0.001). Patients in groups 2, 3, and 4 receiving concizumab had a median annualized bleeding rate of zero episodes. No thromboembolic events occurred upon resuming concizumab therapy, and plasma concizumab levels remained steady.
They concluded that concizumab prophylaxis reduced annualized bleeding rate in patients with hemophilia A or B with inhibitors.