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

Figures & data

Table 1 Approved Dosing Regimens for Long-Term Prophylaxis with rFIXFc or rIX-FP in Adolescent/Adult Patients (≥12 Years) with Hemophilia B

Prophylaxis Regimen	rFIXFc	rIX-FP
Weekly dose-adjusted	50 IU/kg once weekly to start^Citation9,Citation10 Adjust dose based on individual response	35–50 IU/kg once weekly;^Citation16 25–40 IU/kg every 7 days^Citation15
Interval-adjusted	100 IU/kg once every 10 days to start^Citation9,Citation10 Adjust interval based on individual response Patients who are well controlled on a once every 10 days regimen may be treated on an interval of 14 days or longer	Up to 75 IU/kg once every 10 or 14 days^Citation16 For patients >18 years, further extension of the treatment interval may be considered Patients well controlled on an every 7 day regimen may be switched to a 14-day interval at 50–75 IU/kg^Citation15

Abbreviations: rIX-FP, rFIX albumin fusion protein; rFIXFc, recombinant factor IX-Fc fusion protein.

Table 2 Baseline Characteristics in the B-LONG¹² and PROLONG-9FP¹⁷ Phase 3 Studies

	B-LONG		PROLONG-9FP
	Weekly Dose-Adjusted Prophylaxis (n=63)	Interval-Adjusted Prophylaxis (n=29)	Prophylaxis (n=40)	On-Demand (n=23)
Age, years	28 (12–71)^a	33 (12–62)^a	31.6 (15.2)^b	35.3 (11.1)^b
Weight, kg	70.2 (45.2–186.7)^a	76.0 (50.0–128.0)^a	69.6 (14.4)^b	75.1 (20.7)^b
Ethnicity, n (%)
White	41 (65.1)	18 (62.1)	33 (82.5)	19 (82.6)
Asian	7 (11.1)	2 (6.9)	6 (15.0)	4 (17.4)
Black/African American	7 (11.1)	7 (24.1)	1 (2.5)	0
Other	8 (12.7)	2 (6.9)	–	–
Endogenous FIX level, n (%)
<1 IU/dL	50 (79.4)	22 (75.9)
≤1 IU/dL	–	–	35 (87.5)	20 (87.0)
1–2 IU/dL	13 (20.6)	7 (24.1)	–	–
≤2 IU/dL	–	–	40 (100)	23 (100)
Pre-study FIX therapy, n (%)
Prophylaxis	33 (53.2)	15 (51.7)	40 (100)	0
On-demand	29 (46.8)	14 (48.3)	0	23 (100)
Bleeding episodes in prior 12 months
Prior prophylaxis	2.5 (0–21)^a	2.0 (0–7)^a	2.0 (0–4.5)^a, c	–
Prior on-demand	23.0 (6–70)^a	25.0 (10–100)^a	–	23.5 (22–28)^a, d

Notes: ^aMedian (range); ^bMean (SD); ^cPatients assigned to the prophylaxis arm of PROLONG-9FP; ^dPatients assigned to the on-demand arm of PROLONG-9FP, only patients who were previously receiving on-demand treatment were eligible for this group.

Abbreviations: FIX, factor IX; SD, standard deviation.

Table 3 Balance of Baseline Characteristics and Effective Sample Size Following Matching of Patients on a Prior Prophylactic Regimen from the B-LONG Weekly Dose-Adjusted and Interval-Adjusted Prophylaxis Groups and Group 1 of PROLONG-9FP

	Prior to Matching		rFIXFc Adjusted Population
	rIX-FP (n=40)	rFIXFc Unadjusted Population (n=45)^a	Estimate (SD)	ESS, n (%)
Mean (SD) age, years	31.6 (15.2)	34.2 (14.8)	31.6 (15.2)	41.7 (92.6)
Mean (SD) weight, kg	69.6 (14.4)	76.8 (17.4)	69.6 (14.4)	37.4 (83.1)
Mean (SD) prior bleeds	3.4 (3.8)	4.8 (5.9)	3.4 (3.8)	37.9 (92.4)
Proportion of white patients, %	83	67	83	40.2 (89.3)
Final adjusted population
Mean (SD) age, years	–	–	31.6 (15.2)	25.6 (62.6)
Mean (SD) weight, kg	–	–	69.6 (14.4)
Mean (SD) prior bleeds	–	–	3.4 (3.8)
Proportion of white patients, %	–	–	83

Note: ^aData missing for ABR and treatment duration (n=3).

Abbreviations: ABR, annualized bleeding rate; ESS, effective sample size; rIX-FP, rFIX albumin fusion protein; rFIXFc recombinant factor IX-Fc fusion protein; SD standard deviation.

Table 4 Balance of Baseline Characteristics and Effective Sample Size Following Matching of Patients on a Prior on-Demand Regimen from the B-LONG Weekly Dose-Adjusted and Interval-Adjusted Prophylaxis Groups and Group 2 of PROLONG-9FP

	Prior to Matching		rFIXFc Adjusted Population
	rIX-FP (n=23)	rFIXFc Unadjusted Population (n=42)^a	Estimate (SD)	ESS, n (%)
Mean (SD) age, years	35.3 (11.1)	31.3 (13.9)	35.3 (11.1)	32.0 (76.1)
Mean (SD) weight, kg	75.1 (20.7)	75.1 (24.3)	75.1 (20.7)	41.4 (98.5)
Mean (SD) prior bleeds	24.3 (7.3)	28.2 (18.3)	24.3 (7.3)	28.0 (71.7)
Proportion of white patients, %	83	57	83	33.2 (79.1)
Final adjusted population
Mean (SD) age, years	–	–	35.3 (11.1)	10.2 (26.1)
Mean (SD) weight, kg	–	–	75.1 (20.7)
Mean (SD) prior bleeds	–	–	24.3 (7.3)
Proportion of white patients, %	–	–	83

Note: ^aData missing for ABR and treatment duration (n=2).

Abbreviations: ABR, annualized bleeding rate; ESS, effective sample size; rIX-FP, rFIX albumin fusion protein; rFIXFc, recombinant factor IX-Fc fusion protein; SD standard deviation.

Figure 1 Estimated ABR, any bleeding, after matching for all selected baseline variables^†.

Notes: ^†Age, weight, prior bleeds and ethnicity (proportion of white patients); ^‡Data missing for ABR and treatment duration (n=3); ^¶Data from PROLONG-9FP; ^§Data missing for ABR and treatment duration (n=2); ^#Data from PROLONG-9FP, of the 23 patients receiving prior on-demand only 19 patients transitioned to prophylaxis.

Abbreviations: ABR, annualized bleeding rate; CI, confidence interval; ESS, effective sample size; IRR, incidence rate ratio; rIX-FP, rFIX albumin fusion protein; rFIXFc, recombinant factor IX-Fc fusion protein.

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