The FDA has approved emicizumab-kxwh (Hemlibra, Genentech) for routine prophylaxis to prevent or reduce the frequency of bleeding episodes in adults and children with hemophilia A with factor VIII inhibitors––the first new medication for these patients in nearly 20 years.
Nearly one in three people with severe hemophilia A can develop inhibitors to factor VIII replacement therapies, putting them at greater risk for life-threatening bleeds or repeated bleeds that can cause long-term joint damage. In two of the largest pivotal clinical studies for people with hemophilia A with inhibitors, emicizumab-kxwh was shown to substantially reduce bleeds in adults and children.
“People with hemophilia A who develop inhibitors face significant challenges preventing bleeds and typically require infusions of medicine multiple times a week, which can be especially difficult for young children and their families,” said Guy Young, MD, director of the Hemostasis and Thrombosis Program at Children’s Hospital Los Angeles. “This new medicine has been shown to reduce the frequency of bleeds compared to the currently available medicines and only needs to be injected once a week. This could make a meaningful difference for these children.”
In the phase 3 HAVEN 1 study, people 12 years of age or older with hemophilia A with inhibitors who received emicizumab-kxwh prophylaxis had a statistically significant reduction in treated bleeds of 87% (95% confidence interval [CI], 72.3–94.3, P < 0.0001) compared to those who received no prophylaxis. In a first-of-its-kind intra-patient analysis, emicizumab-kxwh prophylaxis resulted in a statistically significant reduction in treated bleeds of 79% (95% CI, 51.4–91.1, P = 0.0003) compared with previous treatment with bypassing agent (BPA) prophylaxis collected in a noninterventional study (NIS) prior to enrollment.
Interim results from the pivotal HAVEN 2 study in children younger than 12 years of age with hemophilia A with inhibitors showed that 87% (95% CI, 66.4–97.2) of children who received emicizumab-kxwh prophylaxis experienced zero treated bleeds. In an intra-patient analysis of 13 children who had participated in the NIS, emicizumab-kxwh prophylaxis resulted in a 99% reduction in treated bleeds compared to previous treatment with a BPA either as prophylaxis (n = 12) or on demand (n = 1).
The most common adverse events (AEs) occurring in 10% or more of people treated with emicizumab-kxwh in pooled studies were injection site reactions, headache and joint pain (arthralgia).
Emicizumab-kxwh will be available in the U.S. shortly. It was reviewed by the FDA under priority review and granted a breakthrough therapy designation. Its robust clinical development program includes two additional phase 3 studies. HAVEN 3 is evaluating emicizumab-kxwh prophylaxis dosed once weekly or once every other week in people 12 years of age or older with hemophilia A without inhibitors to factor VIII. HAVEN 4 is evaluating emicizumab-kxwh prophylaxis dosed every four weeks in people 12 years of age or older with hemophilia A with or without inhibitors.
Emicizumab-kxwh may cause serious side effects when used with aPCC (FEIBA), including thrombotic microangiopathy (TMA) and blood clots (thrombotic events).
Emicizumab-kxwh is a bispecific factor IXa- and factor X-directed antibody. It is designed to bring together factor IXa and factor X, proteins required to activate the natural coagulation cascade and restore the blood clotting process for hemophilia A patients. Emicizumab-kxwh can be administered by an injection of a ready-to-use solution subcutaneously once weekly. Emicizumab-kxwh was created by Chugai Pharmaceutical Co., Ltd., and is being codeveloped by Chugai, Roche (Genentech’s parent company), and Genentech.
Source: Genentech; October 16, 2017.