Pharmacokinetics of a novel extended half‐life glyco<scp>PEG</scp>ylated factor <scp>IX</scp>, nonacog beta pegol (N9‐<scp>GP</scp>) in previously treated patients with haemophilia B: results from two phase 3 clinical trials

Tiede, Andreas; Abdul‐Karim, Fadi W.; Carção, Manuel; Persson, Paula; Clausen, Wan Hui Ong; Kearney, Susan; Matsushita, Tadashi; Négrier, Claude; Oldenburg, Johannes; Santagostino, Elena; Young, Guy

doi:10.1111/hae.13191

Cited by 23 publications

(41 citation statements)

References 23 publications

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“…For all patients, FIX activity remained >0.05 IU/mL for up to 168 hours after single‐dose administration of N9‐GP 40 IU/kg . Geometric mean FIX activity 168 hours postdosing for single dose 40 IU/kg was 0.08 IU/mL (1‐6 years), 0.11 IU/mL (7‐12 years), 0.15 IU/mL (13‐17 years) and 0.17 IU/mL (≥18 years).…”

Section: Resultsmentioning

confidence: 99%

“…When steady‐state FIX activity profiles were predicted using a one‐compartment distribution model, patients treated with N9‐GP 40 IU/kg once‐weekly were predicted to have FIX activity >40% for 5.4 days per week in adolescents and adults (Figure ), and for 2.3 days per week in children …”

Section: Resultsmentioning

confidence: 99%

“…Cumulative time above 15% was predicted to be the entire weekly dosing interval in adolescents and adults (Figure ), and 6.4 days per week in children …”

Section: Resultsmentioning

confidence: 99%

“…N9‐GP has improved PK properties: higher recovery, greater area under the curve (AUC), and a fivefold increase in terminal half‐life compared with standard FIX products . These improvements offer the possibility of maintaining near‐normal (nonhaemophilic) FIX activity levels (>40%; 0.40 IU/mL) with once‐weekly prophylaxis …”

Section: Introductionmentioning

confidence: 99%

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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

Oldenburg¹,

Carção

Lentz

et al. 2018

Haemophilia

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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.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

“…Cumulative time above 15% was predicted to be the entire weekly dosing interval in adolescents and adults (Figure ), and 6.4 days per week in children …”

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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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

Oldenburg¹,

Carção

Lentz

et al. 2018

Haemophilia

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“…Common strategies for enhancing the half-life of a molecule include linkage to the fragment crystallizable (Fc) region of Ig-antibody, to polyethylene glycol (PEG) or to recombinant albumin [23,24,25,26,27,28,29]. …”

Section: Product Choicementioning

confidence: 99%

Hemophilia Care in the Pediatric Age

Bertamino

Riccardi

Banov

et al. 2017

JCM

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Hemophilia is the most common of the severe bleeding disorders and if not properly managed since early infancy can lead to chronic disease and lifelong disabilities. However, it enjoys the most efficacious and safe treatment among the most prevalent monogenic disorders. Hemophilia should be considered in the neonatal period in the case of unusual bleeding or in the case of positive family history. Later, hemophilia should be suspected mainly in males because of abnormal bruising/bleeding or unusual bleeding following invasive procedures—for example, tonsillectomy or circumcision. Prophylactic treatment that is started early with clotting-factor concentrates has been shown to prevent hemophilic arthropathy and is, therefore, the gold standard of care for hemophilia A and B in most countries with adequate resources. Central venous access catheters and arterovenous fistulas play an important role in the management of hemophilia children requiring repeated and/or urgent administration of coagulation factor concentrates. During childhood and adolescence, personalized treatment strategies that suit the patient and his lifestyle are essential to ensure optimal outcomes. Physical activity is important and can contribute to better coordination, endurance, flexibility and strength. The present article focuses also on questions frequently posed to pediatric hematologists like vaccinations, day-care/school access and dental care.

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Clotting factor concentrates for preventing bleeding and bleeding-related complications in previously treated individuals with haemophilia A or B

Olasupo

Lowe

Krishan

et al. 2021

Cochrane Database of Systematic Reviews

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Pharmacokinetics of a novel extended half‐life glycoPEGylated factor IX, nonacog beta pegol (N9‐GP) in previously treated patients with haemophilia B: results from two phase 3 clinical trials

Abstract: N9-GP has the potential to shift previously treated haemophilia B patients from a severe/moderate disease state into a mild- or non-haemophilic range for most of the dosing interval, which is expected to reduce the number of bleeding episodes.

Cited by 23 publications

References 23 publications

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

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

Hemophilia Care in the Pediatric Age

Clotting factor concentrates for preventing bleeding and bleeding-related complications in previously treated individuals with haemophilia A or B

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