Long-term safety and efficacy of N8-GP in previously treated adults and adolescents with hemophilia A: Final results from pathfinder2

Abstract

Background: N8-GP (turoctocog alfa pegol; Esperoct® , Novo Nordisk A/S, Bagsvaerd, Denmark) is a glycoPEGylated human recombinant factor VIII with a half-life of ~1.6-fold of standard FVIII products. pathfinder2 (NCT01480180) was a multi-national, open-label trial of N8-GP in previously treated adolescent and adult patients with severe hemophilia A.

Objective: We report end-of-trial efficacy and safety of N8-GP from pathfinder2.

Methods: pathfinder2 main phase and extension phase part 1 results have been previously reported. During extension phase part 2, patients could switch from N8-GP prophylaxis 50 IU/kg every fourth day (Q4D) or 75 IU/kg once weekly (Q7D), depending on bleeding status. Extension phase part 2 collected long-term safety and efficacy data for all regimens until trial end (first patient in main phase, 30 January 2012; trial end, 10 December 2018).

Results: Overall, 186 patients were exposed to N8-GP for up to 6.6 years (median 5.4 years). The estimated annualized bleeding rate (ABR) was 2.14 (median 0.84) for the Q4D prophylaxis arm and 1.31 (median 1.67) for the Q7D prophylaxis arm. Nearly 30% of patients experienced zero bleeds throughout the entire duration of the trial, the hemostatic response was 83.2% across all treatment arms, and patient-reported outcomes were maintained or slightly improved. No safety concerns were detected.

Conclusion: Data from the completed pathfinder2 trial, one of the largest and longest-running clinical trials to investigate treatment of severe hemophilia A, demonstrate the efficacy and safety of N8-GP in previously treated adolescent and adult patients.

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

Conflict of interest statement

PG has received speaker and consultancy fees from Bayer, CSL Behring, Novo Nordisk, and Pfizer. FAK reports nothing to disclose. LN has received speaker or consultancy fees from Bayer, Baxalta, CSL Behring, Novo Nordisk, Pfizer, and Octapharma. CWY reports nothing to disclose. MSG and AL are employees and stockholders of Novo Nordisk A/S. NC has led research for CSL Behring and received speaker or consultancy fees from LFB, Bayer, Sobi, Novo Nordisk, and Pfizer.

© 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

Trial design, treatment regimen, and disposition of patients throughout pathfinder2 *215 patients were screened, 186 (161 adults, 25 adolescents) were treated with N8‐GP during pathfinder2. **patients with ≤2 bleeding episodes within the last 6 months on the Q4D regimen could switch to Q7D dosing. Patients on Q7D treatment who experienced ≥2 spontaneous bleeds or 1 severe bleed requiring hospitalization over an 8‐week period were switched back to Q4D treatment. Q4D, every fourth day treatment; Q7D, weekly treatment; R, randomization

Figure 2

Proportion of patients in pathfinder2 who experienced no bleeds per year. Results from a post‐hoc analysis of patients who completed the entire trial (n = 110) are shown. Only the initial treatment regimen and first consecutive regimen were included in calculations of the proportion of patients who experienced no yearly bleeds. Q4D, every fourth day treatment; Q7D, weekly treatment