Efficacy and safety of BAY 81-8973, a full-length recombinant factor VIII: results from the LEOPOLD I trial.

Abstract

INTRODUCTION:

BAY 81-8973 (Kovaltry(®) ) is a full-length, unmodified recombinant human factor VIII (FVIII) with the same amino acid sequence as sucrose-formulated recombinant FVIII and is produced using additional advanced manufacturing technologies.

AIM:

To demonstrate efficacy and safety of BAY 81-8973 for treatment of bleeds and as prophylaxis based on two different potency assignments.

METHODS:

In LEOPOLD I (ClinicalTrials.gov identifier, NCT01029340), males aged 12-65 years with severe haemophilia A and ≥150 exposure days received BAY 81-8973 20-50 IU kg(-1) two or three times per week for 12 months. Potency was based on chromogenic substrate assay per European Pharmacopoeia and label adjusted to mimic one-stage assay potency. Patients were randomized for potency sequence and crossed over potency groups after 6 months, followed by an optional 12-month extension. Primary efficacy endpoint was annualized bleeding rate (ABR). Patients also received BAY 81-8973 during major surgeries.

RESULTS:

Sixty-two patients received BAY 81-8973 prophylaxis and were included in the analysis. Median ABR was 1.0 (quartile 1, 0; quartile 3, 5.1) without clinically relevant differences between potency periods. Median ABR was similar for twice-weekly vs. three times-weekly dosing (1.0 vs. 2.0). Haemostasis was maintained during 12 major surgeries. Treatment-related adverse event (AE) incidence was ≤7% overall; no patient developed inhibitors. One patient with risk factors for cardiovascular disease developed a myocardial infarction.

CONCLUSIONS:

BAY 81-8973 was efficacious in preventing and treating bleeding episodes, irrespective of the potency assignment method, with few treatment-related AEs. Caution should be used when treating older patients with cardiovascular risk factors.

• Authors: K Saxena, S Lalezari, J Oldenburg, D Tseneklidou-Stoeter, H Beckmann, M Yoon, M Maas Enriquez
• Journal: Haemophilia : the official journal of the World Federation of Hemophilia (Haemophilia) Vol. 22 Issue 5 Pg. 706-12 (Sep 2016) ISSN: 1365-2516 [Electronic] England
• PMID: 27339736 (Publication Type: Clinical Trial, Phase I, Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial)
• Copyright: © 2016 Bayer. Haemophilia Published by John Wiley & Sons Ltd.

Chemical References

• Coagulants
• F8 protein, human
• Factor VIII

Topics

• Adolescent
• Adult
• Aged
• Child
• Coagulants (adverse effects, pharmacokinetics, therapeutic use)
• Cross-Over Studies
• Dose-Response Relationship, Drug
• Drug Administration Schedule
• Factor VIII (adverse effects, pharmacokinetics, therapeutic use)
• Half-Life
• Hemophilia A (drug therapy, pathology)
• Hemorrhage (prevention & control)
• Humans
• Male
• Middle Aged
• Myocardial Infarction (etiology)
• Orthopedics
• Risk Factors
• Severity of Illness Index
• Treatment Outcome
• Young Adult