Real-world usage and effectiveness of recombinant factor VIII/factor IX Fc in hemophilia A/B: final data from the 24-month, prospective, noninterventional PREVENT study in Germany

Christoph Bidlingmaier; Christine Heller; Florian Langer; Wolfgang Miesbach; Ute Scholz; Johannes Oldenburg; Eveline Nüesch; Helena Palmborg; Elena Santagostino; Andreas Tiede

doi:10.1016/j.rpth.2024.102482

Real-world usage and effectiveness of recombinant factor VIII/factor IX Fc in hemophilia A/B: final data from the 24-month, prospective, noninterventional PREVENT study in Germany

Res Pract Thromb Haemost. 2024 Jun 21;8(5):102482. doi: 10.1016/j.rpth.2024.102482. eCollection 2024 Jul.

Authors

Affiliations

¹ Department of Pediatrics, Dr. von Hauner Children's Hospital, Pediatric Hemophilia Center, LMU Munich, Munich, Germany.
² Department of Pediatric Haemostaseology, University Hospital of Frankfurt, Frankfurt, Germany.
³ University Medical Centre Hamburg-Eppendorf, II. Medical Clinic and Polyclinic, Hamburg, Germany.
⁴ University Hospital, Frankfurt Medical Clinic II, Frankfurt, Germany.
⁵ Center of Coagulation Disorders, Leipzig, Germany.
⁶ University Clinic Bonn, Institute of Experimental Haematology and Transfusion Medicine, Bonn, Germany.
⁷ Sobi, Basel, Switzerland.
⁸ Sobi, Stockholm, Sweden.
⁹ Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany.

Abstract

Background: Real-world experience with efmoroctocog alfa (a recombinant factor [F]VIII Fc fusion protein [rFVIIIFc]) and eftrenonacog alfa (a recombinant factor IX Fc fusion protein [rFIXFc]) is needed to bridge evidence gaps.

Objectives: To describe rFVIIIFc/rFIXFc usage and effectiveness over a 24-month prospective period.

Methods: PREVENT (NCT03055611), a noninterventional study across 25 German hemophilia treatment centers, enrolled previously treated persons with hemophilia A and B (all ages/severities) on individualized rFVIIIFc/rFIXFc prophylaxis before/at enrollment. Primary endpoints included annualized bleeding rate (ABR), injection frequency (IF), and factor consumption (FC). Additionally, up to 12 months of retrospective FVIII/FIX data were collected. Physician and patient satisfaction, and safety outcomes were also assessed.

Results: Overall, 150 patients received ≥1 rFVIIIFc dose and 47 patients received ≥1 rFIXFc dose, with median prospective follow-up of 20.6 and 21.0 months, respectively. rFVIIIFc/rFIXFc demonstrated low median ABR (0.5/1.7), annualized IF (121.8/52.2 injections/y), and FC (4611.7/2423.9 IU/kg) in line with product labels. Compared with previous FVIII/FIX, there was a 56.0% reduction in ABR for rFVIIIFc (rate ratio, 0.44; 95% CI, 0.31-0.64), with no change for rFIXFc (rate ratio, 0.93; 95% CI, 0.66-1.31); rFVIIIFc/rFIXFc reduced annualized IF (rFVIIIFc, mean difference, -31.7; 95% CI, -40.3 to -23.1; rFIXFc, mean difference, -37.3; 95% CI, -46.9 to -27.8), while FC remained stable (rFVIIIFc, +374.1; 95% CI, +46.8 to +701.3; rFIXFc, +503.9; 95% CI, +95.4 to +912.4). Most physicians and patients were satisfied or highly satisfied with rFVIIIFc/rFIXFc. rFVIIIFc/rFIXFc were well tolerated, with no inhibitor development or treatment-related serious adverse events.

Conclusion: Real-world PREVENT data complement phase 3 trials and show that individualized rFVIIIFc/rFIXFc prophylaxis provided stable bleed protection with low IF and maintained FC. Compared with previous FVIII, ABR was considerably reduced with rFVIIIFc, with stable annualized FC. For rFIXFc, bleed protection was maintained vs previous FIX while reducing annualized IF.

Keywords: hemophilia A; hemophilia B; rFIXFc; rFVIIIFc; recombinant fusion protein.