Nonacog beta pegol (N9-GP) in hemophilia B: First report on safety and efficacy in previously untreated and minimally treated patients

被引:15
作者
Chan, Anthony K. [1 ]
Alamelu, Jayanthi [2 ]
Barnes, Chris [3 ]
Chuansumrit, Ampaiwan [4 ]
Garly, May-Lill [5 ]
Meldgaard, Rikke Medom [5 ]
Young, Guy [6 ]
机构
[1] McMaster Univ, McMaster Childrens Hosp, Hamilton, ON, Canada
[2] Evelina London Childrens Hosp, London, England
[3] Royal Childrens Hosp, Melbourne, Vic, Australia
[4] Mahidol Univ, Ramathibodi Hosp, Bangkok, Thailand
[5] Novo Nordisk AS, Soborg, Denmark
[6] Univ Southern Calif, Childrens Hosp Los Angeles, Keck Sch Med, Los Angeles, CA 90007 USA
关键词
factor IX; hemophilia B; nonacog beta pegol; previously untreated patients; prophylaxis; recombinant proteins; FACTOR-IX; INHIBITOR INCIDENCE; HOST ANTIBODIES; CLINICAL-TRIAL; CHILDREN; RECOMMENDATIONS; ANAPHYLAXIS;
D O I
10.1002/rth2.12412
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background/Objective: We report the first analysis of an extended half-life recombinant factor IX, nonacog beta pegol (N9-GP), in previously untreated patients (PUPs) and minimally treated patients with hemophilia B. Methods: Paradigm 6 (Safety and Efficacy of Nonacog Beta Pegol [N9-GP] in Previously Untreated Patients With Haemophilia B) is a multicenter, open-label, single-arm, phase 3 trial. Main inclusion criteria were males aged < 6 years, with hemophilia B with factor IX (FIX) activity <= 2%, who were previously untreated or with <= 3 exposure days (EDs) to FIX-containing products. Patients received N9-GP 40 IU/kg once weekly (prophylaxis) or individualized dosing (preprophylaxis). Bleeds were treated with N9-GP 40 IU/kg (80 IU/kg if severe). The primary end point was incidence of anti-FIX inhibitory antibodies (inhibitors). Secondary end points included safety outcomes and annualized bleeding rate (ABR). Results: At data cutoff (August 31, 2018), 38 patients had been screened, and 37 had received N9-GP (median age, 1.0 years [range, 0-4]). Total in-trial EDs amounted to 2833, representing similar to 65 patient-years. Two (6.1%) of 33 "at-risk" patients (patients with >= 10 EDs plus patients who developed inhibitors) developed high-titer inhibitors and were withdrawn. No other safety concerns, including thromboembolic events, were identified. In the prophylaxis group (n = 28), 67.9% were bleed free; all bleeds (n = 15) were treated with one N9-GP injection; and overall, spontaneous, and traumatic ABRs were low (median ABRs of 0.0, 0.0, and 0.0, respectively; modeled mean ABRs of 0.31, 0.08, and 0.23, respectively). Estimated mean FIX trough activity was 15.0%. Conclusion: We report an inhibitor incidence of 6.1%, which is within the expected range for PUPs with hemophilia B. No other safety concerns were identified; moreover, N9-GP provided effective hemostatic coverage.
引用
收藏
页码:1101 / 1113
页数:13
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