Health Canada has approved emicizumab (Hemlibra®) for use as routine prophylaxis to prevent or reduce bleeding episodes in hemophilia A patients with factor VIII inhibitors.
Emicizumab is a bispecific factor IXa- and factor X-directed antibody. It bridges activated factor IX and factor X to restore the natural function of missing activated factor VIII that is needed for effective blood clotting.
Emicizumab is given as a once-weekly subcutaneous injection.
“Preventing bleeds in patients with hemophilia A can be extremely challenging, usually requiring patients to self-infuse medications multiple times a week, or even daily,” said Jayson Stoffman, MD, of the University of Manitoba in Winnipeg.
“The development of inhibitors adds a significant challenge, with more demanding treatments that are often less effective. Hemlibra offers these patients the chance to effectively reduce the frequency of their bleeds with a once-weekly injection at home. This could significantly improve the quality of life for inhibitor patients, and particularly children and their families.”
The Health Canada approval of emicizumab is based on data from a pair of phase 3 trials—HAVEN 1 and HAVEN 2.
This study enrolled 109 patients (age 12 and older) with hemophilia A and factor VIII inhibitors who were previously treated with bypassing agents (BPAs) on demand or as prophylaxis.
The patients were randomized to receive emicizumab prophylaxis or no prophylaxis. On-demand treatment of breakthrough bleeds with BPAs was allowed.
There was an 87% reduction in treated bleeds with emicizumab compared to no prophylaxis (P<0.0001). And there was an 80% reduction in all bleeds with emicizumab (P<0.0001).
The proportion of patients with 0 treated bleeds was 62.9% among emicizumab recipients and 5.6% among patients who did not receive prophylaxis.
Adverse events (AEs) occurring in at least 5% of patients treated with emicizumab were local injection site reactions, headache, fatigue, upper respiratory tract infection, and arthralgia.
Two patients experienced thromboembolic events (TEs), and 3 had thrombotic microangiopathy (TMA) while receiving emicizumab prophylaxis and more than 100 µ/kg/day of activated prothrombin complex concentrate, on average, for 24 hours or more before the event. Two of these patients had also received recombinant factor VIIa.
Neither TE required anticoagulation therapy, and 1 patient restarted emicizumab. The cases of TMA observed were transient, and 1 patient restarted emicizumab.
There was 1 death, but it was considered unrelated to emicizumab. The patient had developed TMA but died of rectal hemorrhage.
In this single-arm trial, researchers evaluated emicizumab prophylaxis in 60 patients, ages 1 to 17, who had hemophilia A with factor VIII inhibitors.
The efficacy analysis included 57 patients who were younger than 12. The 3 older patients were only included in the safety analysis.
Of the 57 patients, 64.9% had 0 bleeds, 94.7% had 0 treated bleeds, and 98.2% had 0 treated spontaneous bleeds/treated joint bleeds. None of the patients had treated target joint bleeds.
A subset of 23 patients received emicizumab for at least 12 weeks (median treatment duration of 38.1 weeks; range, 12.7 to 41.6 weeks).
Of these 23 patients, 34.8% had 0 bleeds, 87.0% had 0 treated bleeds, and 95.7% had 0 treated spontaneous bleeds/treated joint bleeds.
There were 40 patients who had a total of 201 AEs. The most common of these were viral upper respiratory tract infections (16.7%) and injection site reactions (16.7%).
There were no TEs or TMA events, and none of the patients tested positive for anti-drug antibodies. None of the 7 serious AEs in this trial were considered treatment-related.