Emicizumab Prophylaxis Achieves Positive Results in Patients with Hemophilia A

Investigational drug demonstrates a substantial and clinically meaningful reduction in bleeds related to hemophilia.

Emicizumab prophylaxis achieved positive results in two phase 3 studies for the treatment of hemophilia A with inhibitors to factor VIII.

The investigational drug is a bispecific monoclonal antibody designed to bring together factor IXa and X proteins, which are needed to activate the natural coagulation cascade and restore the blood clotting process, according to a press release. Emicizumab prophylaxis demonstrated substantial and clinically meaningful reduction in bleeds across the HAVEN 1 and HAVEN 2 studies.

The randomized, multi-center, open-label phase 3 HAVEN 1 study evaluated the safety, efficacy, and pharmacokinetics of emicizumab prophylaxis compared with on-demand (no prophylaxis; episodic use only) and prophylactic use of bypassing agents (BPAs) in adults and adolescents with hemophilia with inhibitors to factor VIII.

Included in the study were 109 patients, 12 years or older, with hemophilia with inhibitors to factor VIII who were previously treated with on-demand or prophylactic BPAs.

Participants previously treated with on-demand BPAs were randomized to receive either emicizumab prophylaxis or no prophylaxis. Whereas, patients previously treated with BPA received emicizumab prophylaxis. In a separate arm, patients previously treated with BPA (on-demand or prophylaxis) were enrolled.

The primary endpoint of the study was the number of treated bleeds over time with emicizumab prophylaxis compared with no prophylaxis, according to the release. Secondary endpoints were all bleed rate, joint bleed rate, spontaneous bleed rate, target joint bleed rate, health-related quality of life/health status, intra-patient comparison to bleed rate on their prior prophylaxis regimen or no prophylaxis.

After 31 weeks, 62.9% of patients in the emicizumab prophylaxis arm experienced zero bleeds compared with 5.6% in the on-demand BPAs arm. Reduction in bleed rate with emicizumab prophylaxis was consistent across all secondary endpoints compared with on-demand BPAs, according to the release.

The findings also showed that emicizumab prophylaxis demonstrated a statistically significant and clinically meaningful improvement in health-related quality of life measured at 25 weeks.

In the additional arm, patients previously treated with prophylaxis plus BPAs received emicizumab prophylaxis. The results of the analysis showed a 79% reduction in treated bleeds in patients who received emicizumab prophylaxis compared with treatment with prior prophylaxis plus BPAs.

Reported adverse events (AEs) were injection site reactions, headache, fatigue, upper respiratory tract infection, and arthralgia. Serious AEs were thromboembolic events and thrombotic microangiopathy.

In the single-arm, multicenter, open-label, phase 3 HAVEN 2 study, investigators evaluated the safety, efficacy, and pharmacokinetics of once-weekly subcutaneous administration of emicizumab prophylaxis.

Included in the HAVEN 2 study were 19 patients younger than 12 years of age with hemophilia A with inhibitors to factor VIII, who required treatment with BPAs. Overall, the study will enroll a total of 60 children for the final analysis planned after 52 weeks of treatment with emicizumab prophylaxis, according to the release.

The primary outcomes of the study are the number of treated bleeds over time with emicizumab prophylaxis, safety, pharmacokinetics, health-related quality of life, and proxy health-related quality of life with aspects of caregiver burden.

The findings will be presented at the International Society of Thrombosis and Haemostasis meeting in Berlin, Germany in July.