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 language | English |
|---|---|
| Pages (from-to) | 911-920 |
| Journal | Haemophilia |
| Volume | 24 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - 2018 |
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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 journal › Article
}
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 -