PROTECT VIII kids extension study: Long-term safety and efficacy of BAY 94-9027 (damoctocog alfa pegol) in children with severe haemophilia A

Abstract

Introduction: BAY 94-9027 (damoctocog alfa pegol; an extended half-life PEGylated recombinant factor VIII [FVIII]) demonstrated efficacy and safety in previously treated paediatric patients (PTPs) aged <12 years with severe haemophilia A in the PROTECT VIII Kids study (NCT01775618).

Aim: To evaluate the long-term safety of BAY 94-9027 in PTPs aged <12 years at enrolment.

Methods: In the PROTECT VIII Kids study, boys <12 years with severe haemophilia A were enrolled in two age cohorts (6-<12 years and <6 years) and treated prophylactically twice weekly, every 5 days or every 7 days, with BAY 94-9027 for ≥50 exposure days (EDs). Patients who had completed ≥50 EDs and ≥6 months in the main study or 12-week safety expansion study were eligible to participate in the extension. Primary safety variable was frequency of inhibitor development; main efficacy variable was annualised bleeding rate (ABR).

Results: Of 73 PTPs from the main/expansion studies, 59 (81%) entered the extension phase for a median (range) duration of 5.0 (0.4-5.9) years. Overall, 39 patients completed ≥5 years of treatment. No patients developed FVIII inhibitors/anti-PEG antibodies, and two patients aged <6 years discontinued. Median ABR for total bleeds was 1.5 (<6 years) and 1.9 (6-<12 years). Total ABR improved in the extension vs. the main study. In the last 12 months of treatment, median spontaneous ABR was 0.0 in both age groups.

Conclusions: BAY 94-9027 showed long-term safety and efficacy for the prevention and treatment of bleeds in younger and older paediatric patients with severe haemophilia A.

Keywords: FVIII; adolescents; children; damoctocog alfa pegol; haemophilia A; polyethylene glycol; prophylaxis.

Conflict of interest statement

M.E.M. has acted as a paid consultant, advisor and/or speaker for Bayer, BioMarin, Catalyst, CSL Behring, Grifols, Kedrion, Novo Nordisk, Octapharma, PedNet Foundation, Pfizer, Roche, Sobi and Takeda. T.B. has received honoraria from Bayer and Boehringer Ingelheim. K.F. has acted as a consultant and/or speaker for Baxter/Shire, Bayer, Biogen, CSL Behring, Freeline, Novo Nordisk, Octapharma, Pfizer, Roche and Sobi. K.F. has also received research funding from Baxter/Shire, Bayer, Biogen, Novo Nordisk and Pfizer. M.M.E. is an employee of Bayer. M.S. has acted as a consultant and has received honoraria from Bayer. M.W. and D.T. are both employees of Bayer. S.A. has acted as a consultant for Genentech, Sanofi Genzyme and XaTek, Inc. S.A. has also received research funding, patents and royalties from XaTek, Inc, and has received honoraria from Genentech and Sanofi Genzyme. G.K. has acted as a consultant and/or speaker for Bayer, BioMarin, Novo Nordisk, Pfizer, Roche, Sanofi and Takeda, and has received research funding from Alnylam (Sanofi), Bayer, Pfizer, Roche and Shire. G.K. has also received honoraria from Bayer, BioMarin, CSL Behring, Novo Nordisk, Pfizer, PI Healthcare, Roche, Sanofi and Takeda, and has served on the board of directors or advisory committee for Bayer, BioMarin, Daiichi Sankyo, Novo Nordisk, Pfizer, Roche, Sanofi and Takeda.

© 2021 The Authors. Haemophilia published by John Wiley & Sons Ltd.

Figures

FIGURE 1

PROTECT VIII Kids study design. Regimens were based on treatment at beginning of the extension. ED, exposure day; y, years.

FIGURE 2

Patient disposition and treatment regimens during the PROTECT VIII Kids extension. †Discontinued due to adverse event (n = 1) or other (n = 1). ‡One patient aged 6 to <12 switched from every 5 days to every 7 days. §Two patients aged <6 years switched from every 7 days to twice weekly. ¶Two patients aged <6 years and 4 patients aged 6 to <12 years switched from every 5 days to twice weekly. y, years.

FIGURE 3

Summary of bleeds and BAY 94‐9027 consumption by treatment regimen in all patients (A: aged

FIGURE 4

Summary of bleeds and BAY 94‐9027 consumption by treatment regimen in the subgroup of patients (A: aged