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.

An overview of the pathfinder clinical trials program: Long‐term efficacy and safety of N8‐GP in patients with hemophilia A

“…The hemostatic effect of N8‐GP for treatment of bleeding episodes was confirmed in both the pathfinder2 and pathfinder5 trials 9,10 . In adolescents and adults, 83.2% of all bleeds were successfully treated with N8‐GP, and 94.9% were treated with ≤2 doses.…”

“…Both pathfinder2 (adolescents and adults) and pathfinder5 (children) trials concluded in 2018, and final EOT results covering the entire study periods (main and extension phases) are presented in the accompanying articles within this Supplement 9,10 . In pathfinder2, 186 patients in total (25 adolescents and 161 adults) were exposed to N8‐GP for a total of 66 577 exposure days (EDs), with a total trial time of 785 years.…”

“…Imputed ABRs, in which missing data for patients withdrawing prematurely were replaced with projected values to calculate ABRs as if the patients had remained in the study, are reported in the pathfinder2 EOT analysis 9 . In the pathfinder5 (children) EOT analysis, 10 the estimated ABR (observed data without imputation) was 1.08 (95% CI: 0.81‐1.44) for patients on a twice‐weekly regimen. A comparison of ABR values calculated for the entire trial period with historical ABR data confirmed the prophylactic effect of N8‐GP in both trials.…”

“…In addition, overall ABRs were shown to reduce gradually over the duration of both trials (Figure 2). 9,10 …”

“…Additionally, the pathfinder3 trial, which evaluated the hemostatic efficacy and safety of N8‐GP during surgery, was concluded in December 2018 7,8 . Here, we provide an overview of the pathfinder program, summarize key results from the completed trials (final results from pathfinder2 and pathfinder5 are published together with this article as part of an N8‐GP Supplement 9,10 ), and discuss the future of extended half‐life FVIII molecules in the treatment of patients with hemophilia A.…”