Long-term safety and efficacy of N8-GP in previously treated pediatric patients with hemophilia A: Final results from pathfinder5

Abstract

Background: N8-GP (turoctocog alfa pegol; Esperoct® , Novo Nordisk A/S, Bagsvaerd, Denmark) is a glycoPEGylated, extended half-life human recombinant factor VIII (FVIII).

Objective: Here, we report end-of-trial safety and efficacy results from the completed N8-GP pathfinder5 trial.

Methods: pathfinder5 (NCT01731600) was a multi-national, open-label, single-arm, non-randomized, non-controlled trial in previously treated male patients aged <12 years old with severe hemophilia A that comprised a main and an extension phase. During the main phase, patients received twice-weekly N8-GP 60 IU/kg for 50 exposure days (~26 weeks). During the extension phase, patients received the same regimen until the end of trial (first patient in main phase, 20 February 2013; trial end, 28 September 2018).

Results: Sixty-eight patients were exposed to N8-GP for a median time of ~4.9 years on regimen. Of the 63 patients who started in the extension phase, 62 completed the trial. No FVIII inhibitors (≥0.6 BU) or other safety concerns were detected. The overall estimated annualized bleeding rate was 1.08 (median 0.81), and nearly 20% of patients had no bleeds during the entire trial. The proportion of patients with no annual bleeds increased with time, with 56% of patients experiencing no bleeds and 86% experiencing no spontaneous bleeds during the fourth year of exposure. All baseline target joints of patients who participated in both phases of this trial were resolved in slightly over 2 years.

Conclusion: Overall, data from the completed pathfinder5 trial show that long-term (median 4.9 years) N8-GP treatment was efficacious and well tolerated in previously treated pediatric patients with severe hemophilia A.

Keywords: child; clinical trial; factor VIII; hemophilia A; turoctocog alfa pegol.

Conflict of interest statement

SST received honoraria as a lecturer, symposium speaker, and/or advisory board member from Takeda, Roche, Octapharma, and Novo Nordisk. ME reports nothing to disclose. GK has received research support from Alnylam, Bayer, Opko Biologics, Pfizer, Shire, and honoraria for consultancy from Alnylam, Bayer, Novo Nordisk, Pfizer, Roche, and Takeda. AL and CS are employees and stockholders of Novo Nordisk A/S. SK has received research funding from Novo Nordisk, Grifols, Bayer, Bioverativ, and Daichii Sankyo, and is on advisory boards of Novo Nordisk, Bayer, and Bioverativ.

© 2020 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis.

Figures

FIGURE 1

Patient disposition in the main and extension phases of the pathfinder5 trial. EDs, exposure days; PK, single‐dose pharmacokinetic assessment

FIGURE 2

Patients with zero annual bleeds during the pathfinder5 trial (n = 63). Proportions of patients with zero (A) overall bleeds, (B) spontaneous bleeds, and (C) traumatic bleeds in a given year of treatment. Only patients who participated in both the main and extension phases of the trial were included in this analysis. Patients were analyzed through the fifth year of treatment or until trial end, whichever came first

FIGURE 3

Baseline target joints over time in pathfinder5. Only patients that participated in main and extension phase are included in the analysis (n = 12 patients with 16 target joints). *A single joint with ≥3 bleeding episodes in 6 consecutive months was defined as a target joint. Per protocol, a target joint was no longer considered a target joint if there were no bleeding episodes within 12 consecutive months. **Only patients who participated in the main phase and extension phase of the trial were included in this analysis