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.

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.
Competing Interests: J. Astermark reports research support from Sobi, CSL Behring, Takeda/Shire and Bayer; honoraria for consulting from Octapharma, Novo Nordisk, Pfizer, Bayer, Sobi, CSL Behring, Takeda/Shire, BioMarin, uniQure and Spark Therapeutics; and speaker bureau fees from Octapharma, Novo Nordisk, Pfizer, Bayer, Sobi, CSL Behring, Takeda/Shire and BioMarin. R. Klamroth: reports research funding and honoraria for consulting and lectures from Bayer, BioMarin, Biotest, CSL Behring, Novo Nordisk, Octapharma, Pfizer, Roche, Takeda/Shire and Sobi. Piotr Wojciechowski and S. Aballéa are employees of Creativ-Ceutical, a consultancy company that received funding from Sobi for this research. Z. Hakimi and J. Nazir are employees of Sobi. The authors report no other conflicts of interest in this work.
(© 2021 Astermark et al.)