Nonacog beta pegol in previously treated children with hemophilia B: results from an international open‐label phase 3 trial

Carção, Manuel; Žák, Marek; Karim, F. Abdul; Hanabusa, Hideji; Kearney, Susan; Lu, Meng‐Yao; Persson, Paula; Rangarajan, Savita; Santagostino, Elena

doi:10.1111/jth.13360

Cited by 41 publications

(93 citation statements)

References 20 publications

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“…No patients developed inhibitors and no safety concerns were identified. Another phase III trial investigated safety, efficacy and PK of N9-GP in 25 previously treated boys with hemophilia B (FIX ≤ 2 IU/dL) aged ≤12 years (NCT01467427; Paradigm™5) [34]. All children received prophylaxis with 40 IU/kg N9-GP once weekly for 50 EDs.…”

Section: Extended Half-life Fix Productsmentioning

confidence: 99%

“…All children received prophylaxis with 40 IU/kg N9-GP once weekly for 50 EDs. The median ABRs were 1.0 in the total population, 0.0 in the 0–6 years group and 2.0 in the 7–12 years group with an estimated mean steady-state FIX trough levels of 15.3 and 19.0 IU/dL in the 2 age groups, respectively [34]. For those children who were already in prophylaxis prior to study entry the ABR on study was reduced as compared with the historical one (1.38 vs. 2.51, respectively).…”

Section: Extended Half-life Fix Productsmentioning

confidence: 99%

“…Overall, 86% of bleeds were solved after one single injection. No patient developed inhibitors and no safety concerns were identified [34]. …”

Section: Extended Half-life Fix Productsmentioning

confidence: 99%

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Outcome of Clinical Trials with New Extended Half-Life FVIII/IX Concentrates

Mancuso

Santagostino

2017

JCM

110

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The development of a new generation of coagulation factors with improved pharmacokinetic profile will change the paradigm of treatment of persons with hemophilia (PWH). The standard treatment in PWH is represented by regular long-term prophylaxis that, given intravenously twice or thrice weekly, is associated with a not-negligible burden on patients’ quality of life. The availability of drugs with improved pharmacokinetic profile may improve prophylaxis feasibility and protection against bleeding episodes. This article summarizes the main results obtained from clinical trials with modified factor VIII (FVIII) and factor IX (FIX) molecules. Published literature on new molecules for replacement treatment in hemophilia A and B was retrieved using PubMed search, and all ongoing clinical trials have been researched via . Such new molecules are usually engineered to have a longer plasma half-life than that which has been obtained by chemical modification (i.e., conjugation with polyethylene glycol, PEG) or by creating recombinant fusion proteins. Results from phase I/III studies in previously treated adults and children are now available for the vast majority of new products, including the results of their use in a surgical setting. On the contrary, trials involving previously untreated patients are still ongoing for all and results not yet available.

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Section: Extended Half-life Fix Productsmentioning

confidence: 99%

Section: Extended Half-life Fix Productsmentioning

confidence: 99%

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Outcome of Clinical Trials with New Extended Half-Life FVIII/IX Concentrates

Mancuso

Santagostino

2017

JCM

110

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“…All patients were previously treated males with moderately severe or severe congenital haemophilia B and FIX activity ≤2%. In all trials, N9‐GP was administered intravenously (iv) as bolus injections . Additional information on the N9‐GP protein is provided in the Appendix .…”

Section: Methodsmentioning

confidence: 99%

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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“…A second phase 3 trial included 25 PTPs < 12 years with FIX activity levels 2% [44]. All patients received once-weekly prophylaxis with 40 IU/kg N9-GP for 50 exposure days.…”

Section: Pegylated Fixmentioning

confidence: 99%

Extended Half-Life Factor VIII and Factor IX Preparations

Graf¹

2018

Transfus Med Hemother

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In the last couple of years, several extended half-life factor VIII and factor IX preparations were intensively studied and gained approval. In order to extend half-lives, techniques like fusion to protein conjugates (Fc part of IgG₁ or albumin), chemical modification (PEGylation), and protein sequence modification are implemented. With these techniques, it is possible to extend half-lives of factor IX products 4- to 6- fold, while half-life extension of factor VIII products is limited to 1.5- to 2-fold due to their interaction with von Willebrand factor. Nevertheless, both extended half-life factor VIII and IX products have improved and facilitated prophylactic factor replacement therapy in hemophilia A and B, respectively. Extended half-life factor concentrates pose challenges to coagulation laboratories because accurate therapy monitoring is not possible with all factor activity assays currently used.

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Nonacog beta pegol in previously treated children with hemophilia B: results from an international open‐label phase 3 trial

Cited by 41 publications

References 20 publications

Outcome of Clinical Trials with New Extended Half-Life FVIII/IX Concentrates

Outcome of Clinical Trials with New Extended Half-Life FVIII/IX Concentrates

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

Extended Half-Life Factor VIII and Factor IX Preparations

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