Nonacog beta pegol in adult and paediatric patients: pooled data from the paradigm^TM clinical programme

J. Oldenburg1, M. Carcao2, S. R. Lentz3, J. Mahlangu4, M. Mancuso5, T. Matshushita6, C. Négrier7, W. H. Ong Clausen8, S. Ehrenforth8, G. Young9 (1Bonn, Germany, 2Toronto, Canada, 3Iowa, United States, 4Johannesburg, South Africa, 5Milan, Italy, 6Nagoya, Japan, 7Lyon, France, 8Søborg, Denmark, 9Los Angeles, United States)

Bleeding disorders, coagulation and fibrinolytic factors
Date: 17.02.2017,
Time: 17:15 - 18:15

Objective: Nonacog beta pegol (N9-GP) is an extended half-life recombinant glycoPEGylated factor IX (FIX). We present pooled N9-GP data from 5 completed trials conducted in previously treated paediatric, adolescent and adult haemophilia B patients (PTPs) (1 phase 1; 4 phase 3 trials, including the pivotal randomised trial).

Methods: Results from patients who received N9-GP 40 IU/kg (all ages) or 10 IU/kg (adolescent/adult only) once-weekly prophylaxis including treatment of bleeds are summarised. This analysis includes pharmacokinetics, safety and haemostatic efficacy.

Results: 115 male PTPs (FIX <=2%) were included: 72 adults (18–65 years), 18 adolescents (13–17 years) and 25 children (0–12 years), with a total of 8801 exposure days to N9-GP. In the phase 3 trials, 30 patients received N9-GP at 10 IU/kg/week, 54 patients received 40 IU/kg/week and 15 were treated on-demand. No inhibitors or thromboembolic events were observed. Of 54 (47%) patients treated weekly with 40 IU/kg, 23 (43%) experienced zero bleeding episodes. Median overall annualised bleeding rate (ABR) for all age groups on 40 IU/kg was 1.03 (IQR 0.00–2.89) and median spontaneous ABR was 0.00 (IQR 0.00–0.80). ABR was lower in adolescents/adults randomised to 40 IU/kg than 10 IU/kg (p<0.05). Overall success rate for the treatment of bleeds was 93%; most bleeds (87%) resolved after a single injection. Adults, adolescents and children showed single-dose (40 IU/kg) half-lives of 83, 89 and 73 hours, respectively, and incremental recoveries of 0.023, 0.020 and 0.016 (IU/mL)/(IU/kg), respectively. Estimated mean steady-state FIX trough levels with weekly 40 IU/kg were >=0.15 IU/mL in all age groups. 13 adolescent/adult patients receiving 40 IU/kg N9-GP once-weekly prophylaxis had collectively 20 target joints at study start; by the end of the extension trial, all target joints had resolved. Two questionnaires (EQ-5D VAS and Haem-A-QoL) in adults/adolescents demonstrated significant improvements in quality of life (QoL) from baseline to end of trial in those receiving 40 IU/kg; by the end of the trial, patient QoL scores approached that of the general population.

Conclusion: N9-GP was well tolerated and effective in preventing bleeding at 40 IU/kg once weekly, maintaining FIX activity levels >=15% across all age groups. Once weekly prophylaxis resolved existing target joints and improved patient QoL in adults/adolescents.