The U.S. Food and Drug Administration approved the first-in-class emicizumab-kxwh for routine prophylaxis to prevent or reduce the frequency of bleeding episodes in adult and pediatric patients with hemophilia A and factor VIII (FVIII) inhibitors. The treatment is administered via a once-weekly subcutaneous injection.
The decision was based on the results of two clinical trials. The randomized, multicenter, open-label, phase III HAVEN 1 study included 109 male patients (12-75 years old) with hemophilia A and FVIII inhibitors who previously received on-demand or prophylactic treatment with bypassing agents. Patients were randomized 2:1 to emicizumab-kxwh 3 mg/kg once-weekly for the first four weeks, followed by 1.5 mg/kg once-weekly thereafter, or no prophylaxis. Those receiving emicizumab-kxwh experienced an annualized bleeding rate (ABR) for bleeding events that required treatment with coagulation factors of 2.9 (95% CI 1.7-5.0), compared with 23.3 among those who did not receive prophylaxis (95% CI 12.3-43.9), representing an 87 percent reduction in the rate of treated bleeds (95% CI 72.3-94.3; p<0.0001). Patients receiving emicizumab-kxwh also reported an improvement in hemophilia-related symptoms, including painful swelling and joint pain, and an improvement in physical function, including pain with movement and difficulty walking, compared with those receiving placebo.
The single-arm, multicenter, open-label HAVEN 2 study included 23 male patients (younger than 12 years) with hemophilia A with FVIII inhibitors who were treated at the same dosing schedule used in the HAVEN 1 study. In an interim analysis, 87 percent of patients did not experience a bleeding episode that required treatment, with an ABR of 0.2 (95% CI 0.1-0.6) for treated bleeds. The ABR for all bleeds was 2.9 (95% CI 1.8-4.9).
The most common treatment-related AEs (occurring in 10% or more of patients) included injection-site reaction, headache, and arthralgia.
The drug carries a boxed warning for severe blood clots, which were observed in patients who also received activated prothrombin complex concentrate to treat bleeds for 24 hours or more while taking emicizumab-kxwh.
The drug previously received priority review, breakthrough-therapy, and orphan-drug designations.
Source: U.S. Food and Drug Administration news releases, November 16, 2017.