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

Mindy L Simpson1, Roshni Kulkarni2, Carmen Escuriola Ettingshausen3, Rikke Medom

Meldgaard4, David L Cooper5, Robert Klamroth6

Supplement materials

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Supplementary figure 1 Goodness of fit for (A) predicted FIX activity with N9-GP

compared with observed activity in paradigm 7; (B) Residuals vs time with N9-GP in

paradigm 7; (C) Individual vs population predictions of N9-GP compared with observed

activity in paradigm 7.

Abbreviation: FIX, factor IX.

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Supplementary figure 2 Goodness of fit for (A) predicted FIX activity with rFIXFc

compared with observed activity in paradigm 7; (B) residuals vs time with rFIXFc in

paradigm 7; (C) individual vs population predictions of rFIXFc compared with observed

activity in paradigm 7.

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

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Supplementary figure 3 Predictions of FIX activity with N9-GP compared with

observed activity in paradigm 2.

Abbreviation: FIX, factor IX.

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Supplementary figure 4 Predicted means and confidence limits for simulated

dosing for severe bleeds to achieve FIX activities meeting WFH guidelines2 for (A) N9-

GP 80 IU/kg and for (B) rFIXFc 80 IU/kg followed by 50 IU/kg.

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

of Hemophilia.

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Supplementary figure 5 Predicted means and confidence limits for simulated

dosing for life-threatening bleed (N9-GP vs rFIXFc) to achieve FIX activities to meet

WFH guidelines2 for (A) N9-GP 80 IU/kg followed by 40 IU/kg and (B) rFIXFc 110 IU/kg

followed by three doses of 90 IU/kg and seven doses of 80 IU/kg.

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

of Hemophilia.

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Supplementary figure 6 Predicted means and confidence limits for simulated

dosing for major surgery to achieve FIX activities meeting WFH guidelines2 for (A) N9-

GP 80 IU/kg followed by 40 IU/kg and for (B) rFIXFc 80 IU/kg followed by 50 IU/kg.

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

of Hemophilia.

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