The immunogenicity, safety, and efficacy of N8-GP in previously untreated patients with severe hemophilia A: pathfinder6 end-of-trial results
- PMID: 37597724
- DOI: 10.1016/j.jtha.2023.07.030
The immunogenicity, safety, and efficacy of N8-GP in previously untreated patients with severe hemophilia A: pathfinder6 end-of-trial results
Abstract
Background: The pathfinder6 (NCT02137850) international phase 3 trial examined immunogenicity, safety, and efficacy of the extended half-life factor VIII (FVIII) replacement product N8-GP (turoctocog alfa pegol; Esperoct) in previously untreated patients (PUPs) with hemophilia A.
Objectives: We present end-of trial results for extended PUP N8-GP treatment for up to a median (range) 2.5 (0.0; 7.4) years.
Patients/methods: Longer-term N8-GP treatment in PUPs with hemophilia A was examined. The prophylaxis regimen was ∼60 IU/kg N8-GP i.v. twice weekly, or every 3 or 7 days. The primary endpoint was the incidence of FVIII inhibitors.
Results: Overall, 81 patients received N8-GP and were included in this analysis. The inhibitor incidence was 30.0% (15.7% high-titer [>5 BU]) for the extension phase. Patients had a median (range) 2.9 (0.1; 7.2) years of prophylaxis following the pre-prophylaxis period. During prophylaxis, the median annualized bleeding rate (ABR) (interquartile range) was 1.4 (0.6; 3.5), 13% of patients experienced no bleeding episodes, and 55.1% of patients experienced no spontaneous bleeds. The proportion of patients without any spontaneous bleeding episodes increased after the first year of prophylaxis. The hemostatic success rate in the treatment of bleeding episodes was 87.6%. No additional safety concerns were observed in patients with previously reported observation of temporarily decreased incremental recovery (IR).
Conclusion: Long-term end-of-trial PUP N8-GP prophylaxis data indicate that PUPs respond well to long-term N8-GP treatment. The inhibitor incidence was consistent with previous results. Median ABR during prophylaxis was 1.4. There were no lasting clinical impacts or safety concerns for patients with an observation of temporarily decreased IR.
Keywords: antibodies; factor VIII; hemophilia A; long-term care; neutralizing; pediatrics.
Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.
Conflict of interest statement
Declaration of competing interests G.K. received grant and research support from Alnylam, Bayer, BPL, Opko Biologics, Pfizer, Roche, and Takeda, and participated in advisory boards and received honoraria for consultancy/lectures from Alnylam, Bayer, Biomarine, CSL, Novo Nordisk, Opko Biologics, Pfizer, Takeda, ROCHE, Sanofi, and Uniquore. A.C. participated in the advisory board of Novo Nordisk and received honoraria from Novo Nordisk, Grifols, Takeda, and Roche. Tadashi Matsushita participated in the advisory boards for Takeda, Bayer, Novo Nordisk, Chugai, and Pfizer; received educational and investigational support from Chugai and Novo Nordisk; received honoraria from Takeda, Bayer, Sanofi, Chugai, CSL, JB, KMB, Novo Nordisk, Fujimoto, Sysmex, and Guy Young; and received personal fees from Novo Nordisk during the conduct of the study. C.M. received consultancy or speaker fees from Bayer, Biotest, CSL Behring, Grifols, Novo Nordisk, Roche, and Takeda; received travel support from Bayer, Biotest, CSL Behring, and Novo Nordisk; and received institutional research support from Bayer, Baxalta/Shire/Takeda, Biotest, CSL Behring, Novo Nordisk, and Sobi. V.Y. and M.Z. are employees of Novo Nordisk.