Population Pharmacokinetic Modeling Of On-Demand And Surgical Use Of Nonacog Beta Pegol (N9-GP) And rFIXFc Based Upon The paradigm 7 Comparative Pharmacokinetic Study

Figures & data

Figure 1 Predictions of FIX activity with N9-GP compared with observed activity in paradigm 7.

Abbreviation: FIX, factor IX.

Figure 2 Predictions of FIX activity with rFIXFc compared with observed activity in paradigm 7.

Abbreviations: FIX, factor IX; rFIXFc, recombinant FIX Fc fusion protein.

Table 1 Simulated Number Of Doses And Total Consumption Of N9-GP And rFIXFc For On-Demand Treatment And Surgery

Bleed Type	N9-GP		rFIXFc		N9-GP vs rFIXFc
	# Doses	Total Dose (IU/kg)	# Doses	Total Dose (IU/kg)	# Doses	Total Dose
Severe bleed	1	80	4	230	–75%	–65%
Life-threatening bleed (eg, intracerebral bleed)	5	240	11	940	–55%	–74%
Major surgery	3	160	9	480	–67%	–67%
Major surgery*	4	200	9	480	–55%	–58%

Note: *Sensitivity analysis.

Abbreviation: rFIXFc, recombinant FIX Fc fusion protein.

Figure 3 Simulated dosing for severe bleeds to achieve FIX activities meeting WFH guidelines:¹ N9-GP 80 IU/kg and rFIXFc 80 IU/kg followed by 50 IU/kg.

Abbreviations: FIX, factor IX; rFIXFc, recombinant FIX Fc fusion protein; WFH, World Federation of Hemophilia.

Table 2 Simulated FIX Activity Ranges

FIX Activity (IU/mL)	N9-GP		rFIXFc
	Min	Max	Min	Max
Severe bleed
0 < days ≤3	0.73	1.36	0.46	0.88
Life-threatening bleed (eg, intracerebral bleed)
0 < days ≤7	0.73	1.43	0.63	1.51
7 < days ≤21	0.33	1.16	0.31	1.22
Major surgery
0 < days ≤3	0.73	1.36	0.46	0.88
3 < days ≤6	0.39	0.72	0.39	0.91
6 < days ≤14	0.31	1.06	0.27	0.76
Major surgery*
0 < days ≤3	0.73	1.36
3 < days ≤6	0.75	1.40
6 < days ≤14	0.33	1.43

Note: *Sensitivity analysis.

Abbreviations: FIX, factor IX; rFIXFc, recombinant FIX Fc fusion protein.

Figure 4 Simulated dosing for life-threatening bleeds to achieve FIX activities meeting WFH guidelines:¹ N9-GP 80 IU/kg followed by 40 IU/kg and rFIXFc 110 IU/kg followed by 3 doses of 90 IU/kg and 7 doses of 80 IU/kg.

Abbreviations: FIX, factor IX; rFIXFc, recombinant FIX Fc fusion protein; WFH, World Federation of Hemophilia.

Figure 5 Simulated dosing for major surgery to achieve FIX activities meeting WFH guidelines:¹ N9-GP 80 IU/kg followed by 40 IU/kg and rFIXFc 80 IU/kg followed by 50 IU/kg.

Abbreviations: FIX, factor IX; rFIXFc, recombinant FIX Fc fusion protein; WFH, World Federation of Hemophilia.

Figure 6 Sensitivity analysis for simulated dosing for major surgery to achieve FIX activities to meet WFH guidelines:¹ N9-GP 80 IU/kg followed by 40 IU/kg every 1–3 days during the first week and every week during the second week. rFIXFc 80 IU/kg followed by 50 IU/kg.

Abbreviations: FIX, factor IX; rFIXFc, recombinant FIX Fc fusion protein; WFH, World Federation of Hemophilia.

Srivastava A, Brewer AK, Mauser-Bunschoten EP, et al. Guidelines for the management of hemophilia. Haemophilia. 2013;19(1):e1–47. doi:10.1111/j.1365-2516.2012.02909.x22776238

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