Mahlangu J, et al. - In patients who have hemophilia A without factor VIII inhibitors, researchers studied emicizumab use as prophylaxis in a phase 3, multicenter trial. Compared to no prophylaxis, among patients with hemophilia A without inhibitors, emicizumab prophylaxis administered subcutaneously once weekly or every 2 weeks led to a significantly lower bleeding rate. It was noted no treated bleeding events were seen in more than half the study participants who received prophylaxis. Emicizumab therapy led to a significantly lower bleeding rate than previous factor VIII prophylaxis in an intraindividual comparison.

Methods

• For this investigation, researchers randomly assigned study participants 12 years of age or older who had been receiving episodic treatment with factor VIII in a 2:2:1 ratio to receive a subcutaneous maintenance dose of emicizumab of 1.5 mg per kilogram of body weight per week (group A), 3.0 mg per kilogram every 2 weeks (group B), or no prophylaxis (group C).
• The difference in rates of treated bleeding (group A vs group C and group B vs group C) was the primary end point.
• Study participants who had been receiving factor VIII prophylaxis received emicizumab at a maintenance dose of 1.5 mg per kilogram per week (group D).
• Intraindividual comparisons were performed in those involved in a noninterventional study.

Results

• One hundred fifty-two participants were enrolled in this analysis.
• It was observed that the annualized bleeding rate was 1.5 events (95% confidence interval [CI], 0.9 to 2.5) in group A and 1.3 events (95% CI, 0.8 to 2.3) in group B, compared with 38.2 events (95% CI, 22.9 to 63.8) in group C.
• The rate was 96% lower in group A and 97% lower in group B (P < 0.001 for both comparisons).
• As compared with participants in group C, who all had treated bleeding events, 56% of the participants in group A and 60% of those in group B had no treated bleeding events.
• Emicizumab prophylaxis resulted in an annualized bleeding rate that was 68% lower than the rate with previous factor VIII prophylaxis (P < 0.001) in the intraindividual comparison involving 48 participants.
• Low-grade injection-site reaction was the most frequent adverse event.
• No thrombotic or thrombotic microangiopathy events, development of antidrug antibodies, or new development of factor VIII inhibitors were noted.