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.

Systematic review and analysis of efficacy of recombinant factor IX products for prophylactic treatment of hemophilia B in comparison with rIX-FP

“…Following full-text review, nine articles met the inclusion criteria ( Figure 1). These studies included EHL rFIX products, with one study of rIX-FP (IDELVION 8 ), one study of rFIXFc (Alprolix 9 ), and two studies of N9-GP (Refixia 10,14 ). Standard-acting rFIX products were also included, with two studies of rFIX (BeneFIX 13,15 ), two studies of BAX 326 (Rixubis 16,17 ), and one study of IB1001 (Ixinity 18 ).…”

“…As the results of the adult pivotal trial were separately reported by Windyga et al 16 , the Solano Trujilo et al 17 study was excluded from further review and analysis to prevent including duplicate patients. Similarly, Oldenburg et al 14 reported pooled results from the paradigm trials, and so was excluded from further review to prevent patient duplication, as the results of the adult trial were reported separately by Collins et al 10 .…”

Real‐life experience in switching to new extended half‐life products at European haemophilia centres

“…[8][9][10] Moreover, an ongoing clinical trial with recombinant FIX albumin fusion is investigating whether the dosing interval could be extended to 21 days (clinicaltrials.gov: NCT02053792). 11,[13][14][15][16] These results make such therapies significantly less distressing to the patient (particularly in the case of FIX) and are likely to improve their quality of life. 11,[13][14][15][16] These results make such therapies significantly less distressing to the patient (particularly in the case of FIX) and are likely to improve their quality of life.…”

Optimal trough levels in haemophilia B: Raising expectations

“…Despite these potential differences in extravascular distribution, all EHL FIX products have shown excellent efficacy in clinical trials. [6][7][8] Differences in extravascular distribution observed across FIX products may also be due to variances in measurement parameters.…”