BAY 81-8973 safety and efficacy for prophylaxis and treatment of bleeds in previously treated children with severe haemophilia A: results of the LEOPOLD Kids Trial.

Abstract

INTRODUCTION:

BAY 81-8973, a full-length, unmodified, recombinant factor VIII (FVIII) in development for treatment of haemophilia A, has the same primary amino acid sequence as Bayer's sucrose-formulated recombinant FVIII but is produced with more advanced manufacturing technologies.

AIM:

To demonstrate safety and efficacy of BAY 81-8973 for prophylaxis and treatment of bleeds in previously treated children.

METHODS:

In this phase III, multicentre, open-label, nonrandomized study, boys aged ≤12 years with severe haemophilia A and ≥50 exposure days (EDs) to FVIII products received prophylaxis with BAY 81-8973 25-50 IU kg(-1) ≥2 times weekly for ≥50 EDs. The efficacy endpoint was annualized number of total bleeds. Adverse events (AEs) and immunogenicity were assessed.

RESULTS:

Fifty-one patients were treated (age: <6 years, n = 25; 6-<12 years, n = 26) with a 2× per week (43%) or >2× per week (57%) regimen at study start. Median [quartile 1; quartile 3 (Q1; Q3)] annualized number of bleeds for the combined age groups was 1.90 (0; 6.02) for total bleeds, 0 (0; 2.01) for joint bleeds and 0 (0; 0) for spontaneous bleeds. Median (Q1; Q3) annualized number of total bleeds within 48 h of previous prophylaxis infusion was 1.88 (0; 3.97) for children aged <6 years and 0 (0; 1.96) for children aged 6-<12 years. No drug-related serious AEs or inhibitors were reported.

CONCLUSIONS:

Prophylaxis with BAY 81-8973 using individualized prophylaxis regimens of 2× per week, 3× per week and every-other-day infusions was efficacious in prevention and treatment of bleeds in children with severe haemophilia A. Treatment with BAY 81-8973 was well tolerated.

• Authors: R Ljung, G Kenet, M E Mancuso, V Kaleva, L Rusen, D Tseneklidou-Stoeter, L A Michaels, A Shah, W Hong, M Maas Enriquez, investigators of the LEOPOLD Kids Trial
• Journal: Haemophilia : the official journal of the World Federation of Hemophilia (Haemophilia) Vol. 22 Issue 3 Pg. 354-60 (May 2016) ISSN: 1365-2516 [Electronic] England
• PMID: 26663410 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study)
• Copyright: © 2015 John Wiley & Sons Ltd.

Chemical References

• Coagulants
• F8 protein, human
• Factor VIII

Topics

• Area Under Curve
• Child
• Child, Preschool
• Coagulants (adverse effects, pharmacokinetics, therapeutic use)
• Factor VIII (adverse effects, pharmacokinetics, therapeutic use)
• Half-Life
• Hemophilia A (drug therapy, pathology)
• Hemorrhage (prevention & control)
• Humans
• Infant
• Male
• ROC Curve
• Severity of Illness Index
• Treatment Outcome