Once-weekly prophylaxis with 40 IU/kg nonacog beta pegol (N9-GP) achieves trough levels of >15% in patients with haemophilia B: Pooled data from the paradigm™ trials

Johannes Oldenburg, Manuel Carcao, Steven R. Lentz, Johnny Mahlangu, Maria Elisa Mancuso, Tadashi Matsushita, Claude Négrier, Wan Hui Ong Clausen, Silke Ehrenforth, Guy Young

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Introduction: Prophylaxis with replacement factor IX (FIX) reduces bleeding frequency and improves quality of life in haemophilia B patients. With prophylaxis, the likelihood of bleeding is lowered with increasing trough levels. New products with extended half-life (EHL) can maintain high factor activity levels over prolonged periods, compared with standard FIX products. Aim: To evaluate the safety, efficacy and pharmacokinetics of the new recombinant FIX EHL product, nonacog beta pegol (N9-GP), using pooled data, with a focus on—but not limited to—prophylaxis at 40 IU/kg. Methods: N9-GP has been investigated in males with congenital haemophilia B and FIX activity ≤2% in the paradigm™ clinical trial programme. This analysis includes pooled data from five completed paradigm™ trials conducted in previously treated adults, adolescents and children, focusing on results of prophylaxis with 40 IU/kg once-weekly intravenous dosing. Results: In total, 115 previously treated patients were exposed to N9-GP. Of 54 patients (47%) treated with N9-GP 40 IU/kg once-weekly prophylaxis, 72% experienced no spontaneous bleeds over 1 year. In all patients receiving 40 IU/kg once-weekly, median overall annualized bleeding rate (ABR) was 1.03 (interquartile range 0.00; 2.89); median spontaneous ABR was 0.00 (0.00; 0.80). No patients developed inhibitors. Estimated mean steady-state trough levels with N9-GP 40 IU/kg once-weekly were ≥15% overall; 27.3% in adolescents and adults. Conclusion: N9-GP 40 IU/kg once-weekly was well tolerated and effective in preventing bleeding, maintaining mean FIX activity levels ≥15% across all age groups. N9-GP may provide a new treatment option for preventing bleeding in haemophilia B patients.

Original languageEnglish
Pages (from-to)911-920
JournalHaemophilia
Volume24
Issue number6
DOIs
Publication statusPublished - 2018

Fingerprint

Hemophilia B
Factor IX
Hemorrhage
Half-Life
nonacog beta pegol
Pharmacokinetics
Age Groups
Quality of Life
Clinical Trials
Safety

Keywords

  • factor IX
  • haemophilia B
  • nonacog beta pegol
  • prophylaxis
  • target joint
  • trough level

ASJC Scopus subject areas

  • Hematology
  • Genetics(clinical)

Cite this

Once-weekly prophylaxis with 40 IU/kg nonacog beta pegol (N9-GP) achieves trough levels of >15% in patients with haemophilia B : Pooled data from the paradigm™ trials. / Oldenburg, Johannes; Carcao, Manuel; Lentz, Steven R.; Mahlangu, Johnny; Mancuso, Maria Elisa; Matsushita, Tadashi; Négrier, Claude; Clausen, Wan Hui Ong; Ehrenforth, Silke; Young, Guy.

In: Haemophilia, Vol. 24, No. 6, 2018, p. 911-920.

Research output: Contribution to journalArticle

Oldenburg, J, Carcao, M, Lentz, SR, Mahlangu, J, Mancuso, ME, Matsushita, T, Négrier, C, Clausen, WHO, Ehrenforth, S & Young, G 2018, 'Once-weekly prophylaxis with 40 IU/kg nonacog beta pegol (N9-GP) achieves trough levels of >15% in patients with haemophilia B: Pooled data from the paradigm™ trials', Haemophilia, vol. 24, no. 6, pp. 911-920. https://doi.org/10.1111/hae.13608
Oldenburg, Johannes ; Carcao, Manuel ; Lentz, Steven R. ; Mahlangu, Johnny ; Mancuso, Maria Elisa ; Matsushita, Tadashi ; Négrier, Claude ; Clausen, Wan Hui Ong ; Ehrenforth, Silke ; Young, Guy. / Once-weekly prophylaxis with 40 IU/kg nonacog beta pegol (N9-GP) achieves trough levels of >15% in patients with haemophilia B : Pooled data from the paradigm™ trials. In: Haemophilia. 2018 ; Vol. 24, No. 6. pp. 911-920.
@article{514907e948f5451c95f38c92088e776e,
title = "Once-weekly prophylaxis with 40 IU/kg nonacog beta pegol (N9-GP) achieves trough levels of >15{\%} in patients with haemophilia B: Pooled data from the paradigm™ trials",
abstract = "Introduction: Prophylaxis with replacement factor IX (FIX) reduces bleeding frequency and improves quality of life in haemophilia B patients. With prophylaxis, the likelihood of bleeding is lowered with increasing trough levels. New products with extended half-life (EHL) can maintain high factor activity levels over prolonged periods, compared with standard FIX products. Aim: To evaluate the safety, efficacy and pharmacokinetics of the new recombinant FIX EHL product, nonacog beta pegol (N9-GP), using pooled data, with a focus on—but not limited to—prophylaxis at 40 IU/kg. Methods: N9-GP has been investigated in males with congenital haemophilia B and FIX activity ≤2{\%} in the paradigm™ clinical trial programme. This analysis includes pooled data from five completed paradigm™ trials conducted in previously treated adults, adolescents and children, focusing on results of prophylaxis with 40 IU/kg once-weekly intravenous dosing. Results: In total, 115 previously treated patients were exposed to N9-GP. Of 54 patients (47{\%}) treated with N9-GP 40 IU/kg once-weekly prophylaxis, 72{\%} experienced no spontaneous bleeds over 1 year. In all patients receiving 40 IU/kg once-weekly, median overall annualized bleeding rate (ABR) was 1.03 (interquartile range 0.00; 2.89); median spontaneous ABR was 0.00 (0.00; 0.80). No patients developed inhibitors. Estimated mean steady-state trough levels with N9-GP 40 IU/kg once-weekly were ≥15{\%} overall; 27.3{\%} in adolescents and adults. Conclusion: N9-GP 40 IU/kg once-weekly was well tolerated and effective in preventing bleeding, maintaining mean FIX activity levels ≥15{\%} across all age groups. N9-GP may provide a new treatment option for preventing bleeding in haemophilia B patients.",
keywords = "factor IX, haemophilia B, nonacog beta pegol, prophylaxis, target joint, trough level",
author = "Johannes Oldenburg and Manuel Carcao and Lentz, {Steven R.} and Johnny Mahlangu and Mancuso, {Maria Elisa} and Tadashi Matsushita and Claude N{\'e}grier and Clausen, {Wan Hui Ong} and Silke Ehrenforth and Guy Young",
year = "2018",
doi = "10.1111/hae.13608",
language = "English",
volume = "24",
pages = "911--920",
journal = "Haemophilia",
issn = "1351-8216",
publisher = "Wiley-Blackwell Publishing Ltd",
number = "6",

}

TY - JOUR

T1 - Once-weekly prophylaxis with 40 IU/kg nonacog beta pegol (N9-GP) achieves trough levels of >15% in patients with haemophilia B

T2 - Pooled data from the paradigm™ trials

AU - Oldenburg, Johannes

AU - Carcao, Manuel

AU - Lentz, Steven R.

AU - Mahlangu, Johnny

AU - Mancuso, Maria Elisa

AU - Matsushita, Tadashi

AU - Négrier, Claude

AU - Clausen, Wan Hui Ong

AU - Ehrenforth, Silke

AU - Young, Guy

PY - 2018

Y1 - 2018

N2 - Introduction: Prophylaxis with replacement factor IX (FIX) reduces bleeding frequency and improves quality of life in haemophilia B patients. With prophylaxis, the likelihood of bleeding is lowered with increasing trough levels. New products with extended half-life (EHL) can maintain high factor activity levels over prolonged periods, compared with standard FIX products. Aim: To evaluate the safety, efficacy and pharmacokinetics of the new recombinant FIX EHL product, nonacog beta pegol (N9-GP), using pooled data, with a focus on—but not limited to—prophylaxis at 40 IU/kg. Methods: N9-GP has been investigated in males with congenital haemophilia B and FIX activity ≤2% in the paradigm™ clinical trial programme. This analysis includes pooled data from five completed paradigm™ trials conducted in previously treated adults, adolescents and children, focusing on results of prophylaxis with 40 IU/kg once-weekly intravenous dosing. Results: In total, 115 previously treated patients were exposed to N9-GP. Of 54 patients (47%) treated with N9-GP 40 IU/kg once-weekly prophylaxis, 72% experienced no spontaneous bleeds over 1 year. In all patients receiving 40 IU/kg once-weekly, median overall annualized bleeding rate (ABR) was 1.03 (interquartile range 0.00; 2.89); median spontaneous ABR was 0.00 (0.00; 0.80). No patients developed inhibitors. Estimated mean steady-state trough levels with N9-GP 40 IU/kg once-weekly were ≥15% overall; 27.3% in adolescents and adults. Conclusion: N9-GP 40 IU/kg once-weekly was well tolerated and effective in preventing bleeding, maintaining mean FIX activity levels ≥15% across all age groups. N9-GP may provide a new treatment option for preventing bleeding in haemophilia B patients.

AB - Introduction: Prophylaxis with replacement factor IX (FIX) reduces bleeding frequency and improves quality of life in haemophilia B patients. With prophylaxis, the likelihood of bleeding is lowered with increasing trough levels. New products with extended half-life (EHL) can maintain high factor activity levels over prolonged periods, compared with standard FIX products. Aim: To evaluate the safety, efficacy and pharmacokinetics of the new recombinant FIX EHL product, nonacog beta pegol (N9-GP), using pooled data, with a focus on—but not limited to—prophylaxis at 40 IU/kg. Methods: N9-GP has been investigated in males with congenital haemophilia B and FIX activity ≤2% in the paradigm™ clinical trial programme. This analysis includes pooled data from five completed paradigm™ trials conducted in previously treated adults, adolescents and children, focusing on results of prophylaxis with 40 IU/kg once-weekly intravenous dosing. Results: In total, 115 previously treated patients were exposed to N9-GP. Of 54 patients (47%) treated with N9-GP 40 IU/kg once-weekly prophylaxis, 72% experienced no spontaneous bleeds over 1 year. In all patients receiving 40 IU/kg once-weekly, median overall annualized bleeding rate (ABR) was 1.03 (interquartile range 0.00; 2.89); median spontaneous ABR was 0.00 (0.00; 0.80). No patients developed inhibitors. Estimated mean steady-state trough levels with N9-GP 40 IU/kg once-weekly were ≥15% overall; 27.3% in adolescents and adults. Conclusion: N9-GP 40 IU/kg once-weekly was well tolerated and effective in preventing bleeding, maintaining mean FIX activity levels ≥15% across all age groups. N9-GP may provide a new treatment option for preventing bleeding in haemophilia B patients.

KW - factor IX

KW - haemophilia B

KW - nonacog beta pegol

KW - prophylaxis

KW - target joint

KW - trough level

UR - http://www.scopus.com/inward/record.url?scp=85053802723&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85053802723&partnerID=8YFLogxK

U2 - 10.1111/hae.13608

DO - 10.1111/hae.13608

M3 - Article

AN - SCOPUS:85053802723

VL - 24

SP - 911

EP - 920

JO - Haemophilia

JF - Haemophilia

SN - 1351-8216

IS - 6

ER -