BAY 94-9027, a PEGylated recombinant factor VIII, exhibits a prolonged half-life and higher area under the curve in patients with severe haemophilia A: Comprehensive pharmacokinetic assessment from clinical studies.

Abstract

INTRODUCTION:

Recombinant factor VIII (rFVIII) products with extended half-lives, such as BAY 94-9027, can potentially maintain higher FVIII levels for longer periods of time, thus providing improved bleeding protection vs standard-acting FVIII products.

AIM:

To characterize the pharmacokinetic (PK) profile of BAY 94-9027 from phase 1, phase 2/3 (PROTECT VIII) and phase 3 (PROTECT VIII Kids) clinical trials in adults, adolescents and children with severe haemophilia A METHODS: Patients with severe haemophilia A (FVIII <1%) with >50 FVIII exposure days (EDs) and no history of inhibitors were included in the phase 1 (18-65 years, ≥150 EDs), PROTECT VIII (12-65 years, ≥150 EDs) and PROTECT VIII Kids (<12 years, >50 EDs) trials. PK parameters were assessed following a 25-IU/kg or 60-IU/kg BAY 94-9027 dose in the phase 1 study after the first and repeated infusion, in PROTECT VIII after the first and repeated 60-IU/kg infusion and in PROTECT VIII Kids after a single 60-IU/kg infusion. The chromogenic assay was used to assess FVIII activity.

RESULTS:

Compared with sucrose-formulated rFVIII, BAY 94-9027 had reduced clearance that resulted in a ~1.4-fold increase in half-life and dose-normalized area under the curve (AUC). The BAY 94-9027 PK profile was comparable after single- and repeated-dose administrations. Dose-proportional increases were observed between 25- and 60-IU/kg administrations. BAY 94-9027 PK characteristics were age dependent, consistent with other FVIII products.

CONCLUSIONS:

BAY 94-9027 shows an extended half-life and increased AUC vs standard-acting FVIII products. These PK characteristics will result in higher FVIII levels for longer duration.

• Authors: A Shah, T Coyle, S Lalezari, K Fischer, B Kohlstaedde, H Delesen, S Radke, L A Michaels
• Journal: Haemophilia : the official journal of the World Federation of Hemophilia (Haemophilia) Vol. 24 Issue 5 Pg. 733-740 (Sep 2018) ISSN: 1365-2516 [Electronic] England
• PMID: 29963724 (Publication Type: Journal Article)
• Copyright: © 2018 The Authors. Haemophilia Published by John Wiley & Sons Ltd.

Chemical References

• BAY 94-9027
• Polyethylene Glycols
• Factor VIII

Topics

• Adolescent
• Adult
• Aged
• Child
• Child, Preschool
• Factor VIII (pharmacokinetics, pharmacology, therapeutic use)
• Hemophilia A (drug therapy, pathology)
• Humans
• Infant
• Infant, Newborn
• Middle Aged
• Polyethylene Glycols (pharmacokinetics, pharmacology, therapeutic use)
• Young Adult