Recombinant factor IX-Fc fusion protein (rFIXFc) demonstrates safety and prolonged activity in a phase 1/2a study in hemophilia B patients

Amy D. Shapiro, Margaret V. Ragni, Leonard A. Valentino, Nigel S. Key, Neil C. Josephson, Jerry S Powell, Gregory Cheng, Arthur R. Thompson, Jaya Goyal, Karen L. Tubridy, Robert T. Peters, Jennifer A. Dumont, Donald Euwart, Lian Li, Bengt Hallén, Peter Gozzi, Alan J. Bitonti, Haiyan Jiang, Alvin Luk, Glenn F. Pierce

Research output: Contribution to journalArticle

113 Citations (Scopus)

Abstract

Current factor IX (FIX) products display a half-life (t 1/2) of ∼ 18 hours, requiring frequent intravenous infusions for prophylaxis and treatment in patients with hemophilia B. This open-label, dose-escalation trial in previously treated adult subjects with hemophilia B examined the safety and pharmacokinetics of rFIXFc. rFIXFc is a recombinant fusion protein composed of FIX and the Fc domain of human IgG 1, to extend circulating time. Fourteen subjects received a single dose of rFIXFc; 1 subject each received 1, 5, 12.5, or 25 IU/kg, and 5 subjects each received 50 or 100 IU/kg. rFIXFc was well tolerated, and most adverse events were mild or moderate in intensity. No inhibitors were detected in any subject. Dose-proportional increases in rFIXFc activity and Ag exposure were observed. With baseline subtraction, mean activity terminal t 1/2 and mean residence time for rFIXFc were 56.7 and 71.8 hours, respectively. This is ∼ 3-fold longer than that reported for current rFIX products. The incremental recovery of rFIXFc was 0.93 IU/dL per IU/kg, similar to plasma-derived FIX. These results show that rFIXFc may offer a viable therapeutic approach to achieve prolonged hemostatic protection and less frequent dosing in patients with hemophilia B. The trial was registered at www.clinicaltrials.gov as NCT00716716.

Original languageEnglish (US)
Pages (from-to)666-672
Number of pages7
JournalBlood
Volume119
Issue number3
DOIs
StatePublished - Jan 19 2012

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Hemophilia B
Safety
Factor IX
Recombinant Fusion Proteins
Pharmacokinetics
factor IX Fc fusion protein
Hemostatics
Intravenous Infusions
Half-Life
Labels
Immunoglobulin G
Plasmas
Recovery

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Recombinant factor IX-Fc fusion protein (rFIXFc) demonstrates safety and prolonged activity in a phase 1/2a study in hemophilia B patients. / Shapiro, Amy D.; Ragni, Margaret V.; Valentino, Leonard A.; Key, Nigel S.; Josephson, Neil C.; Powell, Jerry S; Cheng, Gregory; Thompson, Arthur R.; Goyal, Jaya; Tubridy, Karen L.; Peters, Robert T.; Dumont, Jennifer A.; Euwart, Donald; Li, Lian; Hallén, Bengt; Gozzi, Peter; Bitonti, Alan J.; Jiang, Haiyan; Luk, Alvin; Pierce, Glenn F.

In: Blood, Vol. 119, No. 3, 19.01.2012, p. 666-672.

Research output: Contribution to journalArticle

Shapiro, AD, Ragni, MV, Valentino, LA, Key, NS, Josephson, NC, Powell, JS, Cheng, G, Thompson, AR, Goyal, J, Tubridy, KL, Peters, RT, Dumont, JA, Euwart, D, Li, L, Hallén, B, Gozzi, P, Bitonti, AJ, Jiang, H, Luk, A & Pierce, GF 2012, 'Recombinant factor IX-Fc fusion protein (rFIXFc) demonstrates safety and prolonged activity in a phase 1/2a study in hemophilia B patients', Blood, vol. 119, no. 3, pp. 666-672. https://doi.org/10.1182/blood-2011-07-367003
Shapiro, Amy D. ; Ragni, Margaret V. ; Valentino, Leonard A. ; Key, Nigel S. ; Josephson, Neil C. ; Powell, Jerry S ; Cheng, Gregory ; Thompson, Arthur R. ; Goyal, Jaya ; Tubridy, Karen L. ; Peters, Robert T. ; Dumont, Jennifer A. ; Euwart, Donald ; Li, Lian ; Hallén, Bengt ; Gozzi, Peter ; Bitonti, Alan J. ; Jiang, Haiyan ; Luk, Alvin ; Pierce, Glenn F. / Recombinant factor IX-Fc fusion protein (rFIXFc) demonstrates safety and prolonged activity in a phase 1/2a study in hemophilia B patients. In: Blood. 2012 ; Vol. 119, No. 3. pp. 666-672.
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AU - Shapiro, Amy D.

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AU - Valentino, Leonard A.

AU - Key, Nigel S.

AU - Josephson, Neil C.

AU - Powell, Jerry S

AU - Cheng, Gregory

AU - Thompson, Arthur R.

AU - Goyal, Jaya

AU - Tubridy, Karen L.

AU - Peters, Robert T.

AU - Dumont, Jennifer A.

AU - Euwart, Donald

AU - Li, Lian

AU - Hallén, Bengt

AU - Gozzi, Peter

AU - Bitonti, Alan J.

AU - Jiang, Haiyan

AU - Luk, Alvin

AU - Pierce, Glenn F.

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N2 - Current factor IX (FIX) products display a half-life (t 1/2) of ∼ 18 hours, requiring frequent intravenous infusions for prophylaxis and treatment in patients with hemophilia B. This open-label, dose-escalation trial in previously treated adult subjects with hemophilia B examined the safety and pharmacokinetics of rFIXFc. rFIXFc is a recombinant fusion protein composed of FIX and the Fc domain of human IgG 1, to extend circulating time. Fourteen subjects received a single dose of rFIXFc; 1 subject each received 1, 5, 12.5, or 25 IU/kg, and 5 subjects each received 50 or 100 IU/kg. rFIXFc was well tolerated, and most adverse events were mild or moderate in intensity. No inhibitors were detected in any subject. Dose-proportional increases in rFIXFc activity and Ag exposure were observed. With baseline subtraction, mean activity terminal t 1/2 and mean residence time for rFIXFc were 56.7 and 71.8 hours, respectively. This is ∼ 3-fold longer than that reported for current rFIX products. The incremental recovery of rFIXFc was 0.93 IU/dL per IU/kg, similar to plasma-derived FIX. These results show that rFIXFc may offer a viable therapeutic approach to achieve prolonged hemostatic protection and less frequent dosing in patients with hemophilia B. The trial was registered at www.clinicaltrials.gov as NCT00716716.

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