Pharmacokinetic-Guided Reduction of Emicizumab in Patients with Congenital Hemophilia a in the Netherlands: Interim Analysis from the Dosemi Study

• Published in: Blood 2024-11, Vol.144 (Supplement 1), p.127-127
• Main Authors: Van Der Zwet, Konrad, Cnossen, Marjon H., Moenen, Floor CJI, Schols, Saskia EM, Ypma, Paula F, den Exter, Paul L., Hooimeijer, Louise, Coppens, Michiel, Mathôt, Ron A.A., Donners, Anouk A.M.T., Janssen, Alexander, Kruis, Ilmar, Van Beers, Eduard J., Eckhardt, Corien L., Urbanus, Rolf T., Van Vulpen, Lize Fie Ditteke, Schutgens, Roger EG, Fischer, Kathelijn
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2024-193995

Background: While prophylactic emicizumab therapy is highly effective in preventing bleeding in hemophilia A and generally well-tolerated, the high costs impose a significant financial burden on healthcare systems. Several case series have suggested that current bodyweight-based dosing of emicizumab could be safely reduced, providing similar effectiveness at a lower cost. Aim: Determine whether individualized PK-guided reduced dosing of emicizumab targeting a Ctrough emicizumab concentration of 30±5 μg/mL is non-inferior to conventional bodyweight-based dosing in the prevention of bleeding in hemophilia A patients. Methods: The DosEmi study is an ongoing phase IV, multicenter, prospective, open-label, crossover study comparing 12 months of conventional dosing of emicizumab vs 12 months of PK-guided reduced dosing targeting at concentrations of 30±5 μg/mL (ClinicalTrial.gov - NCT06320626). Study participants were recruited from eight Dutch hemophilia treatment centers from September 1st 2022 onwards. Eligible participants have severe or moderate congenital hemophilia A (FVIII < 6 IU/mL) with and without FVIII-inhibitors; receiving conventional dosing of emicizumab (according to label of 6 mg/kg/4 weeks at varying intervals) for a duration of ≥ 12 months prior to inclusion with good bleeding control, defined as: no spontaneous joint/muscle bleeds in the previous six months and/or a maximum of two treated (traumatic) bleeds in the previous six months. Emicizumab concentrations were determined by a validated liquid chromatography-tandem mass spectrometry method after 12 months on conventional dosing, only patients with an emicizumab trough levels of ≥ 40 μg/mL were eligible for dose reduction. Patients with emicizumab trough levels of 25-39 μg/mL continued their current dose regimen and were followed observationally for 12 months. Patients with emicizumab trough levels of < 25 μg/mL were adjusted in dosing regimen according to local protocol. The interim analysis was scheduled to compare the proportion of patients without treated bleeds during six months of follow-up on conventional dosing to six months on PK-guided dosing using survival analysis, with a predefined non-inferiority criterion of an absolute risk difference of