Abstract

Introduction

The short half-life of standard factor VIII (FVIII) products means that frequent injections (3 to 4 times/week) are needed for effective prophylaxis in patients with hemophilia A. N8-GP (turoctocog alfa pegol), an extended half-life glycoPEGylated recombinant FVIII developed for the prophylaxis and treatment of bleeds in patients with hemophilia A, allows for less frequent dosing. Bleed frequency is an important outcome measure in hemophilia, particularly when choosing a dosing regimen that best suits a broad range of patients.

Objectives

To summarize annualized bleeding rate (ABR) data from 2 clinical trials of N8-GP in patients with severe hemophilia A.

Methods

Patients with severe hemophilia A (FVIII <1%) were enrolled into the pathfinder comprehensive clinical trial program:

  • pathfinder 2 main phase

    • Adults/adolescents ≥12 years, N8-GP 50 IU/kg every 4 days (Q4D) or 20-75 IU/kg on demand

  • pathfinder 2 extension phase

    • Adults/adolescents ≥12 years, randomized to receive N8-GP 50 IU/kg Q4D or 75 IU/kg once weekly (Q7D)

    • Patients with ≤2 bleeds in the last 6 months were eligible for randomization

  • pathfinder 5 main phase

    • Children <12 years, N8-GP 60 IU/kg (50-75 IU/kg) twice weekly.

ABR was analyzed using a Poisson-regression model on the number of bleeds per patient, allowing for over-dispersion and using log-planned observation duration as an offset to allow for different treatment durations, with age cohort as a factor for pathfinder 5. Median and estimated Poisson mean ABR data from the 2 trials were summarized for overall, spontaneous, traumatic, joint, and muscle bleeds.

Results

For adults/adolescents receiving N8-GP 50 IU/kg Q4D (pathfinder 2 main phase) and those randomized to receive 50 IU/kg Q4D or 75 IU/kg Q7D (pathfinder 2 extension), median overall ABRs were 1.18, 0.00, and 0.00, respectively (Table). Corresponding median ABRs were:

  • For spontaneous bleeds 0.00, 0.00, and 0.00

  • For traumatic bleeds 0.00, 0.00, and 0.00

  • For joint bleeds 0.85, 0.00, and 0.00

  • For muscle bleeds 0.00, 0.00, and 0.00.

For children (aged 0-11 years) receiving 60 IU/kg twice weekly (pathfinder 5), median overall, spontaneous, traumatic, joint, and muscle ABRs were 1.95, 0.00, 0.00, 0.00, and 0.00, respectively. Poisson estimated mean ABR data for all bleed types are also shown in the Table.

Conclusion

N8-GP provides effective prophylactic protection in adult/adolescent and pediatric patients with severe hemophilia A, as demonstrated by low ABRs in phase 3 clinical trials. For patients of all ages, N8-GP enables simplicity in the choice of prophylaxis dose and dosing frequency with no need for pharmacokinetic-tailored dosing.

Disclosures

Chowdary:Bayer, CSL Behring, Novo Nordisk, Pfizer, and SOBI (publ): Research Funding; Baxalta (Shire), Baxter, Biogen Idec, CSL Behring, Freeline, Novo Nordisk, Pfizer, Roche, Shire, and SOBI: Consultancy. Hvitfeldt Poulsen:Lecturer on Nordic meeting on EHL FVIII (SOBI): Other: Lecturer ; Primary investigator and national coordinator on clinical trials from Bayer Health Care: Other: Primary Investigator and national coordinator; Nordic advisory boards (Bayer Health Care, Roche): Membership on an entity's Board of Directors or advisory committees; Chaired an educational haemophilia symposium for nurses: Other: Chair. Escobar:Bayer, CSL Behring, Genentech, Hemabiologics, Kedrion, Novo Nordisk, Octapharma, Pfizer and Shire: Consultancy; Pfizer: Research Funding. Kearney:Bayer, Bioverativ, Daiichi Sankyo, Grifols and Novo Nordisk: Research Funding; Bayer, Bioverativ and Novo Nordisk: Membership on an entity's Board of Directors or advisory committees. Chitlur:Novo Nordisk Inc: Consultancy; Baxter, Bayer, Biogen Idec, and Pfizer: Honoraria. Klamroth:Baxalta (Shire), Bayer, CSL Behring, Novo Nordisk, Octapharma, Pfizer, Shire, and SOBI: Research Funding; Baxalta (Shire), Bayer, CSL Behring, Novo Nordisk, Octapharma, Pfizer, Shire, and SOBI: Consultancy. Negrier:Novo Nordisk: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; CSL Behring: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Bayer: Honoraria, Research Funding; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Baxalta/Shire: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Alnylam: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Octapharma: Honoraria, Research Funding; LFB: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Sobi/Bioverativ: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Clausen:Novo Nordisk: Employment. Driessler:Novo Nordisk: Employment. Landorph:Novo Nordisk: Employment. Santagostino:Kedrion: Membership on an entity's Board of Directors or advisory committees; Bioverativ: Membership on an entity's Board of Directors or advisory committees; Grifols: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Octapharma: Membership on an entity's Board of Directors or advisory committees; Shire: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; Bayer: Membership on an entity's Board of Directors or advisory committees; Sobi: Membership on an entity's Board of Directors or advisory committees; Novo Nordisk: Membership on an entity's Board of Directors or advisory committees; CSL Behring: Membership on an entity's Board of Directors or advisory committees.

Author notes

*

Asterisk with author names denotes non-ASH members.