Photo from Novo Nordisk
N9-GP (Rebinyn)
GLASGOW—Nonacog beta pegol (N9-GP) has a better pharmacokinetic (PK) profile than recombinant factor IX-Fc fusion protein (rFIXFc), according to researchers.
In a phase 1 trial, adults with hemophilia B who received a single dose of N9-GP achieved greater total factor IX exposure than those treated with rFIXFc, and N9-GP had a longer half-life.
Seven days after injection, factor IX activity was 6-fold greater in patients treated with N9-GP than in those treated with rFIXFc at the same dose.
“As a clinician, I know first-hand how challenging it can be to help people living with hemophilia B reach their treatment goals and be adequately protected from bleeding,” said Carmen Escuriola Ettingshausen, MD, of Haemophilia Centre Rhein Main in Frankfurt-Mörfelden, Germany.
“These data will help us better understand the different treatment options and choose the appropriate treatment for each patient.”
Dr Ettingshausen presented the data at the World Federation of Hemophilia (WFH) 2018 World Congress during the late-breaking abstract session on Monday.
The research was sponsored by Novo Nordisk A/S, the company marketing N9-GP (as Rebinyn or Refixia). N9-GP is an extended half-life factor IX molecule intended for replacement therapy in patients with hemophilia B.
In the Paradigm7 trial, researchers compared the PK profiles of N9-GP and rFIXFc (Alprolix).
Fifteen previously treated adult males with congenital hemophilia B (factor IX activity ≤2%) received single injections (50 IU/kg) of N9-GP and rFIXFc with at least 21 days between doses.
One patient was excluded from the analysis due to intake of a prohibited medication (an rFIXFc product that was not Alprolix). Two other patients were excluded from some analyses because they missed 2 PK time points.
The primary endpoint was dose-normalized area under the factor IX activity-time curve from 0 to infinity (AUC0-inf,norm).
The estimated AUC0-inf,norm (n=12) was significantly higher for N9-GP than rFIXFc—9656 IU*h/dL and 2199 IU*h/dL, respectively (ratio=4.39, P<0.0001).
There were significant differences for secondary endpoints as well.
The maximum factor IX activity dose-normalized to 50 IU/kg (n=14) was 91 IU/dL with N9-GP and 45 IU/dL with rFIXFc (ratio=2.02, P<0.001).
The incremental recovery at 30 minutes (n=14) was 1.7 (IU/dL)/(IU/kg) with N9-GP and 0.8 (IU/dL)/(IU/kg) with rFIXFc (ratio=2.20, P<0.001).
The terminal half-life (n=12) was 103.2 hours with N9-GP and 84.9 hours with rFIXFc (ratio=1.22, P<0.001).
The clearance (n=12) was 0.52 mL/h/kg with N9-GP and 2.25 mL/h/kg with rFIXFc (ratio=0.23, P<0.001).
The factor IX activity at 168 hours (n=12) was 19 IU/dL with N9-GP and 3 IU/dL with rFIXFc (ratio=5.80, P<0.001).
None of the patients developed inhibitors, and no safety concerns were identified, according to Novo Nordisk. The company did not provide additional safety information.