“Emicizumab (trade name Hemlibra, emicizumabkxwh, ACE910, RO5534262) is a bispecific IgG4 mAb targeting Factors IXa and X. On November 16, 2017, the drug (emicizumabkxwh) was approved by Food and Drug Administration (FDA) approved to prevent or reduce the frequency of bleeding episodes in adult and pediatric patients with hemophilia.  In two clinical studies for people with hemophilia A with inhibitors, HEMLIBRA was shown to substantially reduce bleeds in adults and children.”

On November 16, 2017, the Food and Drug Administration approved emicizumab-kxwh (HEMLIBRA, Genentech, Inc.) for routine prophylaxis to prevent or reduce the frequency of bleeding episodes in adult and pediatric patients with hemophilia A (congenital factor VIII deficiency) with factor VIII inhibitors.

Approval was based on data from two clinical trials—an adult and adolescent trial (HAVEN 1) and a pediatric trial (HAVEN 2). HAVEN 1 (NCT02622321) was a randomized, multicenter, open-label, phase 3 trial in 109 adult and adolescent males (aged 12 to 75 years and >40 kg) with hemophilia A with FVIII inhibitors who previously received either episodic (on-demand) or prophylactic treatment with bypassing agents. Patients on prior episodic treatment were randomized 2:1 to weekly emicizumab-kxwh prophylaxis (3 mg/kg once weekly for the first 4 weeks followed by 1.5 mg/kg once weekly, thereafter) or no prophylaxis. Patients randomized to no prophylaxis could switch to emicizumab-kxwh prophylaxis after 24 weeks. For patients receiving emicizumab-kxwh prophylaxis, the annualized bleeding rate (ABR) requiring treatment with coagulation factors was 2.9 (95% CI; 1.7, 5.0) compared with 23.3 (95% CI: 12.3, 43.9) for patients not receiving prophylaxis corresponding to an 87% ABR reduction (95% CI: 72.3%, 94.3%), p<0.0001. In addition, improvements in patient-reported hemophilia-related symptoms and physical functioning in patients receiving emicizumab-kxwh prophylaxis were observed.

HAVEN 2 (NCT02795767) was a single-arm, multicenter, open-label, clinical trial in pediatric males (age < 12 years, or 12-17 years who weigh 40 kg) with hemophilia A with FVIII inhibitors. Patients received emicizumab-kxwh prophylaxis at the dose and schedule described above. In 23 patients evaluated at the interim analysis, ABR for treated bleeds was 0.2 (95% CI: 0.1, 0.6). ABR for all bleeds was 2.9 (95% CI: 1.8, 4.9).

The most common adverse reactions (occurring in ≥ 10% of patients taking emicizumab-kxwh) are injection site reactions, headache, and arthralgia. Cases of thrombotic microangiopathy and thrombotic events were reported when on average a cumulative amount of >100 U/kg/24 hours of activated prothrombin complex concentrate (aPCC) was administered for 24 hours or more to patients receiving emicizumab-kxwh prophylaxis. The prescribing information contains a boxed warning to monitor for thrombotic microangiopathy and thrombotic events when aPCC is administered. If symptoms occur, aPCC should be discontinued and emicizumab-kxwh should be suspended.

The recommended dose of emicizumab-kxwh is 3 mg/kg by subcutaneous injection once weekly for the first 4 weeks, followed by 1.5 mg/kg once weekly.

Resource: https://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm585650.htm