In an indirect comparison of data across clinical trials for management of hemophilia A, treatment with recombinant factor VIII-Fc fusion protein (rFVIIIFc) appeared to show greater efficacy as a prophylaxis therapy than use of emicizumab every 4 weeks (Q4W) did. Results of the analysis were published in the Journal of Blood Medicine.
Primary prophylaxis may protect against joint damage and joint or other hemorrhages in patients with hemophilia A. The current standard of care for primary prophylaxis in severe hemophilia A is replacement factor VIII.
The researchers noted that head-to-head trials comparing rFVIIIFc and emicizumab for hemophilia A prophylaxis do not currently exist. They performed an indirect, matching-adjusted comparison of these agents using data from the A-LONG trial for use of rFVIIIFc as well as the HAVEN 3 and HAVEN 4 trials for use of emicizumab, with emicizumab being given once per week (Q1W), every 2 weeks (Q2W), or Q4W. Matching was based on patient baseline characteristics, and comparisons involved mean annualized bleeding rate (ABR), proportion of patients with no bleeds, and safety.
Mean ABR across matched populations was statistically similar with rFVIIIFc and with any dosing schedule of emicizumab. In the comparison of rFVIIIFc and Q1W-administered emicizumab, mean ABRs were 2.73 vs 2.93, respectively (incidence rate ratio [IRR], 0.93 [95% CI, 0.63-1.39]). When comparing rVIIIFc and Q4W-administered emicizumab, mean ABRs were 2.75 and 4.50, respectively (IRR, 0.61 [95% CI, 0.37-1.02]).
Treatment with rFVIIIFc was associated with a higher proportion of patients (51.2%) with no bleeds than was seen using Q4W-administered emicizumab (29.3%; odds ratio, 2.53 [95% CI, 1.09-5.89]). Results for this metric with rFVIIIFc were similar to those with emicizumab given using Q1W or Q2W schedules.
Mean numbers of adverse events per participant were 1.9 with rFVIIIFc, 3.7 to 4.0 with emicizumab given Q1W, 4.1 with emicizumab given Q2W, and 3.6 with emicizumab given Q4W. Injection site reactions occurred in 20% to 32% of patients receiving emicizumab across dosing schedules, while they were not reported with rFVIIIFc.
“This indirect treatment comparison indicates that rFVIIIFc individualized prophylaxis is more efficacious than emicizumab administered Q4W for the proportion of patients with zero bleeds,” the researchers concluded in their report. ABR trends favored rFVIIIFc, although rates appeared to be similar across treatments for this outcome.
Disclosures: Some authors have declared affiliations with or received grant support from the pharmaceutical industry. Please refer to the original study for a full list of disclosures.
Klamroth R, Wojciechowski P, Aballéa S, et al. Efficacy of rFVIIIFc versus emicizumab for the treatment of patients with hemophilia A without inhibitors: matching-adjusted indirect comparison of A-LONG and HAVEN trials. J Blood Med. 2021;12:115-122. doi:10.2147/JBM.S288283