Long-Term Safety and Efficacy of Nonacog Beta Pegol (N9-GP) Administered for at Least 5 Years in Previously Treated Children with Hemophilia B

Abstract

Long-term safety and efficacy data of extended half-life factor IX (FIX) prophylaxis in children with hemophilia B (HB) are sparse. paradigm 5 is a multinational, open-label, single-arm, phase III trial assessing once-weekly (40 IU/kg) prophylactic nonacog beta pegol (N9-GP) in previously treated patients (PTPs) aged ≤ 12 years with HB (FIX activity ≤ 2%). Primary endpoint: incidence of anti-FIX inhibitory antibodies (≥ 0.6 Bethesda Units). We present a 5-year analysis (N = 25, including remaining patients with ≥ 5 years' follow-up) and compare with a 1-year analysis (≥ 52 weeks' exposure). The main phase enrolled 25 children; 22 entered the extension phase; 17 remained in trial at data cutoff. Median treatment period: 5.6 years/patient; median total number of N9-GP exposure days: 290.0/patient. No patients developed anti-FIX inhibitory antibodies. No other safety concerns, including thromboembolic events, were reported. Neurological examinations have not revealed any new abnormal findings. Sixteen (64.0%) patients remained free from spontaneous bleeds; all bleeds were mild/moderate in severity; 93.0% were controlled with 1 to 2 N9-GP injections. No intracranial hemorrhages were reported. Annualized bleeding rates (ABRs) were very low at 5 years (median/Poisson-estimated mean overall ABR: 0.66/0.99), having decreased from the 1-year analysis (1.00/1.44). Median/Poisson-estimated mean spontaneous ABRs for the 1- and 5-year analyses: 0.00/0.45 and 0.00/0.33. Mean FIX trough activity at 5 years: 17.9%. Mean polyethylene glycol plasma concentration reached steady state at 6 months, increasing slightly over time, in line with increased FIX trough activity. N9-GP administered for ≥ 5 years shows favorable long-term safety and efficacy in PTPs with HB (FIX activity ≤ 2%).

Conflict of interest statement

M.C. has received grant/research support from: Baxalta (Shire), Bayer, Biogen, Novo Nordisk and Pfizer, has been a consultant for Baxalta/Shire/Takeda, Bayer, Biogen/Bioverativ/Sanofi, CSL Behring, Grifols, Novo Nordisk, Octapharma, Pfizer, and Roche, and is a member of speaker bureaus of Baxalta (Shire), Bayer, Biogen, CSL Behring, Grifols, Novo Nordisk, Octapharma, Pfizer, and Roche.S.K. has received grant/research support from: local principal investigator (PI) research funding for Bayer, Bioverativ, Daiichi Sankyo, Grifols, and Novo Nordisk, and is a member of speaker bureaus/advisory boards for Bayer, Bioverativ, and Novo Nordisk.M.Y.L. has no conflict of interest.M.T. has served on advisory boards for Bayer, Bioverativ, Chugai, and Novo Nordisk; has received research support in clinical trials as a local PI for Bioverativ, Chugai, CSL Behring, and Novo Nordisk, and has received speaker's fees from Bayer, Bioverativ, Chugai, CSL Behring, Novo Nordisk, and Shire.D.R. and C.S. are employees of Novo Nordisk A/S, Søborg, Denmark.E.S. has served on advisory boards for Bayer, Bioverativ, CSL Behring, Grifols, Kedrion, Novo Nordisk, Octapharma, Pfizer, Roche, Shire/Takeda, SOBI, Spark, and Uniqure and has been a member of speaker bureaus for Bayer, CSL Behring, Grifols, Kedrion, Novo Nordisk, Pfizer, Roche, Shire/Takeda, and SOBI.

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