PB1160 - WAPPS-Hemo as a tool for optimizing prophylaxis with extended half-life FIX in patients with severe or moderate hemophilia B

Tuesday, July 12, 2022

6:30 PM – 7:30 PM

Location: Exhibition

Presentation Format: In-Person

Presenting Author(s)

Timea Szanto

consultant
Coagulation Disorders Unit, Department of Hematology, Helsinki University Hospital Comprehensive Cancer Center and University of Helsinki, Helsinki, Finland
Helsinki, Uusimaa, Finland

Co-Author(s)

Riitta Lassila, MD, PhD

Professor of Coagulation Medicine
Helsinki University Hospital, Coagulation Disorders Unit, Department of Haematology, Comprehensive Cancer Centre, and Research Program Unit in System Oncology, University of Helsinki, Helsinki, Finland
Helsinki, Uusimaa, Finland
VN

Vuokko Nummi

Internal medicine, MD, PhD
Coagulation Disorders Unit, Comprehensive Cancer Center, Helsinki University Hospital
Helsinki, Uusimaa, Finland
AI

Alfonso Iorio

Professor
Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON
Hamilton, Ontario, Canada
AL

Anna-Elina Lehtinen

Adjunct Professor, Head of the Unit
Coagulation Disorders Unit, Department of Hematology, Helsinki University Hospital Comprehensive Cancer Center and University of Helsinki, Helsinki, Finland
Helsinki, Uusimaa, Finland

Background: The Web-Accessible Population Pharmacokinetic Service—Hemophilia (WAPPS-Hemo) is a web-based database application developed to individualize coagulation factor replacement therapy.

Aims: The impact of switching from standard half-life (SHL) rFIX product (Nonacog alfa, Benefix) to extended half-life (EHL) rFIX-Fc (Eftrenonacog alfa, Alprolix) or N9-GP (Nonacog beta pegol, Refixia) was evaluated on FIX pharmacokinetics (PK), weekly dosage and prophylactic infusion frequency.

Methods: FIX activity was measured by one-stage assay at least twice between two doses during regular EHL prophylaxis. PK analyses were performed using the WAPPS-Hemo application and dosing estimations aimed to maintain trough levels of 5 IU/dL.

Results: Thirteen patients with hemophilia B were switched to EHL-FIX, six to rFIX-Fc (2 severe and 4 moderate phenotypes; median age 25.5 y, range 18-60 y) and seven to N9-GP (3 severe and 4 moderate; median age 53 y, range 40-74 y). Median dose of FIX concentrate for the PK analysis was 46 IU/kg for rFIX-Fc and 52 IU/kg for N9-GP. The median half-life was extended to 124-125 hours for both FIX-Fc and N9-GP compared with 22-38 h using rFIX (Benefix). The median time to maintain trough levels at least 5 IU/dL was extended by 4.9 days for rFIX-Fc (p = 0.0007), but 13 days for N9-GP (p = 0.0017) . After switching to EHL-FIX, the median weekly dosage decreased by 10% for rFIX-Fc (p = 0.7) while by 66% for N9-GP (p = 0.002). Prophylactic infusion frequency could be reduced in almost all: 5/6 (83%) for rFIX-Fc and 6/7 (86%) for N9-GP. In the rFIX-Fc group, 3 patients currently infuse once every 2 weeks. In the N9-GP group, 5 patients infuse once every 2 weeks and 1 patient once every 23 days.

Conclusion(s): Switch from SHL to N9-GP resulted in more significant reduction in weekly dosage and infusion frequency in comparison with rFIX-Fc. The clinical effects of rFIX-Fc and N9-GP will be evaluated in the future.