Positive Results for Emicizumab in Phase III Studies in Hemophilia A with Inhibitors

Emicizumab decreases incidence of bleeding episodes by 87 percent in patients with Hemophilia A with inhibitors, according to new data from the HAVEN 1 study. Data from HAVEN 1 was released at the International Society of Thrombosis and Hemostasis (ISTH) and published in the New England Journal of Medicine. Interim data from HAVEN 2 study were presented at ISTH as well.

Emicizumab is a bispecific monoclonal antibody designed to bring together factors IXa and X, proteins which help activate the natural coagulation cascade and restore the blood clotting process, according to Genentech, who is co-developing the treatment with Roche and Chugai Pharmaceuticals.

HAVEN 1 compared emicizumab with on-demand (no prophylaxis) and prophylaxis use of bypassing agents (BPAs) in adults and adolescents with hemophilia A with inhibitors.

The trial included 109 patients 12 years of age or older with hemophilia A with inhibitors to factor VIII, who were previously treated with BPAs on-demand or as prophylaxis.

The primary endpoint was treated bleeds, and results showed a statistically significant and clinically meaningful reduction in bleed rate of 87 percent with emicizumab prophylaxis compared with on-demand treatment with BPAs.

All 12 secondary endpoints were positive, including an intra-patient comparison that showed emicizumab reduced bleed rate by 79 percent compared to prior prophylactic BPAs.

“This is the most significant advancement I have seen during my 20 years working in the field of hemophilia,” said Guy Young, MD, director of the Hemostasis and Thrombosis Program and lead physician for study efforts at Children’s Hospital Los Angeles in a release. Young was part of the international team involved in the HAVEN 1 study.

Furthermore, a clinically meaningful and statistically significant improvement in health-related quality of life (HRQoL), measured at 25 weeks, using two validated instruments (Haem-A-QoL and EQ-5D-5L), was observed.

Interim results from the single arm HAVEN 2 study in children younger than 12 years of age with hemophilia A with inhibitors who received emicizumab prophylaxis are consistent with the positive results from the HAVEN 1 study.

After a median observation time of 12 weeks, the study showed only one of 19 children receiving emicizumab reported a treated bleed. There were no reported joint or muscle bleeds.

The drug is administered by injection subcutaneously once a week. Current treatment for people with hemophilia A with a severe bleeding phenotype is prophylactic intravenous infusions of factor VIII two to three times weekly.

According to the companies, data from both HAVEN 1 and HAVEN 2 have been submitted for approval consideration to the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA). The FDA granted Breakthrough Therapy Designation for emicizumab in adults and adolescents with hemophilia A with inhibitors in September 2015. Additional studies evaluating emicizumab in people with hemophilia A both with and without inhibitors are ongoing.