FDA Grants Breakthrough Therapy Designation to Emicizumab-kxwh

The US Food and Drug Administration (FDA) has announced that it granted Breakthrough Therapy Designation to emicizumab-kxwh (Hemlibra, Genentech), for patients with hemophilia A without factor VIII inhibitors.

The therapy was previously granted a Priority Review designation in August 2017, and was approved in November 2017 for prophylaxis or reduction of the frequency of bleeding episodes in adults and children with hemophilia A with factor VIII inhibitors, based on results from the HAVEN 1 and 2 studies.

The standard factor VIII replacement therapy is inhibited for roughly one-third of all patients with hemophilia A, limiting the treatment options and raising the risk of long-term damage and life-threatening bleeds.

“HEMLIBRA is the first medicine to show superior efficacy compared to factor VIII prophylaxis, the standard of care for people with hemophilia A without inhibitors, in an intra-patient comparison,” said Sandra Horning, MD, the chief medical officer and head of Global Product Development at Genentech, in a statement. “We look forward to working with health authorities to make HEMLIBRA available to people without inhibitors as soon as possible, and we are excited to share this news with the community as we join in celebrating World Hemophilia Day.”

The agency’s decision was made based on data from the HAVEN 3 study, a phase 3 trial in patients aged 12 years and older with hemophilia A without inhibitors. Patients previously treated with on-demand factor VIII were randomized 2:2:1 to 3 groups: Group A, to receive subcutaneous 3 mg/kg/wk emicizumab-kxwh prophylactically for 4 weeks, followed by 1.5 mg/kg/wk until the end of the trial; Group B, to receive subcutaneous prophylaxis at 3 mg/kg/wk for 4 weeks, followed by 3 mg/kg/2wks until the end of study; and Group C, to receive no prophylaxis.

A fourth group, Group D, consisting of those previously treated with factor VIII prophylaxis, received subcutaneous prophylaxis at 3 mg/kg/wk for 4 weeks, followed by 1.5 mg/kg/wk until the end of the study.

The therapy, when used prophylactically either weekly or biweekly, showed a statistically significant reduction in treated bleeds in comparison to no prophylaxis. When used once-weekly and compared intra-patient, the Genentech product was revealed to be superior to prior factor VIII preventive therapy, and significantly reduced treated bleeds.

The most common adverse events from emicizumab-kxwh were injection-site reactions, and no previously unobserved events occurred. There were no instances of thrombotic microangiopathy or thrombotic events in the study, according to Genentech.