Pharmacokinetic-guided dose reduction of emicizumab in congenital hemophilia A: interim analysis of the DosEmi study

Background Emicizumab provides effective prophylaxis for hemophilia A (HA), but its cost puts a burden on health care systems. Pharmacokinetic (PK)-pharmacodynamic analyses suggest that emicizumab is effective at lower trough concentrations (Ctrough) than the mean 55 µg/mL reported with conventional dosing. Objectives To perform an interim analysis comparing bleeding control during 6 months of conventional emicizumab dosing vs PK-guided dosing in participants with HA, targeting a Ctrough of 25-35 µg/mL. Methods The DosEmi study (NCT06320626) is an ongoing multicenter, open-label, crossover Dutch trial. Eligible participants were aged =16 years using emicizumab for =12 months with good bleeding control (=2 treated bleeds/6 months, none spontaneous). This planned interim analysis compared 6 months’ bleeding on conventional dosing with PK-guided dosing. Study continuation criteria were =15% decrease in the proportion of participants without treated bleeds, maximum of 2 spontaneous bleeds overall, and <1.0 increase in bleeds/y (annualized bleeding rate). Results In 26 participants with severe HA, PK-guided dosing reduced emicizumab consumption by 39% (range, 13%-50%). The proportion of participants without treated bleeds was 69% with conventional dosing vs 58% with PK-guided dosing (risk difference, +11%; P = .254); the proportion without joint bleeds remained stable at 85% vs 88%, respectively (risk difference, -4%; P = .500). The annualized bleeding rate remained low (0.7 vs 0.9; P = .132), including 1 spontaneous muscle bleed (emicizumab concentration 52.5 µg/mL). Conclusion These interim results suggest that bleeding control with PK-guided reduced emicizumab dosing (target Ctrough 25-35 µg/mL) is similar to conventional dosing. All prespecified criteria for study continuation and inclusion of participants aged <16 years were met.