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Emicizumab (Hemlibra)
The US Food and Drug Administration (FDA) has approved use of emicizumab-kxwh (Hemlibra®), a bispecific factor IXa- and factor X-directed antibody.
Emicizumab is approved as routine prophylaxis to prevent or reduce the frequency of bleeding episodes in adults and children who have hemophilia A and factor VIII (FVIII) inhibitors.
Emicizumab can be self-administered once-weekly via subcutaneous injection.
The labeling for emicizumab contains a boxed warning noting that patients who received emicizumab in conjunction with activated prothrombin complex concentrate developed thrombotic microangiopathy (TMA) and thromboembolic events (TEs).
Therefore, patients should discontinue prophylactic use of bypassing agents (BPAs) the day before starting prophylaxis with emicizumab.
The FDA granted the approval of emicizumab to Genentech, Inc. The agency granted the application for emicizumab priority review, and the product received breakthrough therapy and orphan drug designations.
Access to emicizumab
According to Genentech, emicizumab will be available shortly.
The company said it will be offering comprehensive services to help minimize barriers to access and reimbursement. Patients can call 866-436-5427 (866-HEMLIBRA) for more information.
For people who qualify, Genentech plans to offer patient assistance programs through Genentech Access Solutions. More information is available at 866-422-2377 (866-4ACCESS) or http://www.Genentech-Access.com.
Emicizumab trials
The biologics license application for emicizumab was supported by results from a pair of phase 3 studies—HAVEN 1 and HAVEN 2.
Results from HAVEN 1 were published in NEJM and presented at the 26th ISTH Congress in July. Interim results from HAVEN 2 were presented at ISTH as well.
HAVEN 1
The study enrolled 109 patients (age 12 and older) with hemophilia A and FVIII inhibitors who were previously treated with 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 a significant reduction in treated bleeds of 87% with emicizumab prophylaxis compared to no prophylaxis (95% CI: 72.3; 94.3, P<0.0001). And there was an 80% reduction in all bleeds with emicizumab (95% CI: 62.5; 89.8, P<0.0001).
Adverse events 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 TEs, and 3 had TMA while receiving emicizumab prophylaxis and more than 100 u/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.
HAVEN 2
In this single-arm trial, researchers evaluated emicizumab prophylaxis in children younger than 12 years of age who had hemophilia A with FVIII inhibitors.
The interim efficacy analysis, after at least 12 weeks of treatment, included 23 children.
After a median observation time of 38.1 weeks, 87% (95% CI: 66.4; 97.2) of children who received emicizumab experienced 0 treated bleeds. The percentage with 0 treated or non-treated bleeds was lower, at 34.8% (95% CI: 16.4; 57.3).
The most common adverse events (observed in at least 10% of patients) were mild injection site reactions and nasopharyngitis. No TEs or TMAs were observed.
HAVEN 3 and 4
Emicizumab is now being studied in 2 additional phase 3 trials.
In HAVEN 3, researchers are evaluating emicizumab prophylaxis dosed once weekly or once every other week in patients age 12 and older with hemophilia A without FVIII inhibitors.
In HAVEN 4, researchers are evaluating emicizumab prophylaxis dosed every 4 weeks in patients age 12 and older with hemophilia A, with or without inhibitors.
