Efficacy of rFIXFc versus rIX-FP for the Treatment of Patients with Hemophilia B: Matching-Adjusted Indirect Comparison of B-LONG and PROLONG-9FP Trials

Jan Astermark; Piotr Wojciechowski; Samuel Aballéa; Zalmai Hakimi; Jameel Nazir; Robert Klamroth

doi:10.2147/JBM.S312885

Efficacy of rFIXFc versus rIX-FP for the Treatment of Patients with Hemophilia B: Matching-Adjusted Indirect Comparison of B-LONG and PROLONG-9FP Trials

J Blood Med. 2021 Jul 14:12:613-621. doi: 10.2147/JBM.S312885. eCollection 2021.

Authors

Jan Astermark¹, Piotr Wojciechowski², Samuel Aballéa³, Zalmai Hakimi⁴, Jameel Nazir⁴, Robert Klamroth⁵

Affiliations

¹ Department of Translational Medicine, Lund University, and Department of Hematology, Oncology and Radiation Physics, Skåne University Hospital, Malmö, Sweden.
² Creativ-Ceutical, Krakow, Poland.
³ Creativ-Ceutical, Rotterdam, the Netherlands.
⁴ Swedish Orphan Biovitrum AB, Stockholm, Sweden.
⁵ Department of Internal Medicine, Hemophilia Treatment Centre, Vivantes Klinikum im Friedrichshain, Berlin, Germany.

Abstract

Purpose: In patients with hemophilia B, treatment with extended half-life (EHL) recombinant factor IX allows for longer dosing intervals while providing equal or superior bleeding protection compared with standard half-life products. This enables flexible, individualized treatment schedules, which reduce the burden of prophylaxis and improve patient outcomes. This analysis compared the efficacy of recombinant factor IX Fc fusion protein (rFIXFc) and recombinant factor IX albumin fusion protein (rIX-FP), two EHL therapies approved for prophylaxis and treatment of bleeding in hemophilia B.

Patients and methods: Matching-adjusted indirect treatment comparison (MAIC) was used to adjust the between-treatment differences in baseline characteristics. Individual patient data for rFIXFc (B-LONG) were matched to aggregated data for rIX-FP (PROLONG-9FP) followed by statistical comparison for estimated annualized bleeding rate (ABR) using a Poisson regression model with adjustment for over dispersion. Data were analyzed according to treatment regimen prior to study entry: prior prophylaxis (rFIXFc, n=48; rIX-FP, n=40) or prior episodic treatment (n=43 and n=19, respectively). Relative treatment effects are presented as incidence rate ratios (IRR) with 95% confidence intervals (CI).

Results: After adjustment for baseline characteristics, estimated ABR observed for rFIXFc and rIX-FP was not significantly different in patients on prior prophylaxis (1.87 versus 1.58; IRR 1.18, 95% CI 0.67-2.10) or prior episodic (2.25 versus 2.22; IRR 1.01 95% CI 0.40-2.57) regimens.

Conclusion: This MAIC analysis shows that the estimated ABR for rFIXFc-treated patients from B-LONG was similar to that of rIX-FP-treated patients from PROLONG-9FP and, therefore, indicates that the two EHL therapies provide similar efficacy when used as prophylaxis for patients with hemophilia B. Trough levels differ between the two products (1-3% [targeted] versus 20% [observed], respectively), suggesting that trough level is not a surrogate indicator when ABR is used as a criterion for clinical efficacy when comparing these FIX products in hemophilia B.

Keywords: annualized bleeding rate; comparative effectiveness research; factor IX Fc fusion protein; factor IX deficiency; rIX-FP fusion protein; treatment outcome.