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BAY 81-8973 Efficacy and Safety in Previously Untreated and Minimally Treated Children with Severe Hemophilia A : The LEOPOLD Kids Trial

Ljung, Rolf LU orcid ; Chan, Anthony K C ; Glosli, Heidi ; Afonja, Olubunmi ; Becker, Bastian ; Tseneklidou-Stoeter, Despina ; Mancuso, Maria Elisa ; Saulyte-Trakymiene, Sonata and Kenet, Gili (2023) In Thrombosis and Haemostasis 123(1). p.27-39
Abstract

INTRODUCTION:  BAY 81-8973, a full-length recombinant factor VIII for hemophilia A treatment, has been extensively evaluated in previously treated patients in the LEOPOLD (Long-Term Efficacy Open-Label Program in Severe Hemophilia A Disease) clinical trials.

AIM:  To assess BAY 81-8973 efficacy and safety when used for bleed prophylaxis and treatment in previously untreated/minimally treated patients (PUPs/MTPs).

METHODS:  In this phase III, multicenter, open-label, uncontrolled study, PUPs/MTPs (<6 years old) with severe hemophilia A received BAY 81-8973 (15-50 IU/kg) at least once weekly as prophylaxis. Primary efficacy endpoint was the annualized bleeding rate (ABR) within 48 hours after prophylaxis infusion. Adverse... (More)

INTRODUCTION:  BAY 81-8973, a full-length recombinant factor VIII for hemophilia A treatment, has been extensively evaluated in previously treated patients in the LEOPOLD (Long-Term Efficacy Open-Label Program in Severe Hemophilia A Disease) clinical trials.

AIM:  To assess BAY 81-8973 efficacy and safety when used for bleed prophylaxis and treatment in previously untreated/minimally treated patients (PUPs/MTPs).

METHODS:  In this phase III, multicenter, open-label, uncontrolled study, PUPs/MTPs (<6 years old) with severe hemophilia A received BAY 81-8973 (15-50 IU/kg) at least once weekly as prophylaxis. Primary efficacy endpoint was the annualized bleeding rate (ABR) within 48 hours after prophylaxis infusion. Adverse events and immunogenicity were assessed. Patients who developed inhibitors were offered immune tolerance induction (ITI) treatment in an optional extension phase.

RESULTS:  Fifty-two patients were enrolled, with 43 patients (mean age: 13.6 months) treated. Median (interquartile range) ABR for all bleeds within 48 hours of prophylaxis infusion was 0.0 (0.0-1.8) among patients without inhibitors (
n  = 20) and 0.0 (0.0-2.2) among all patients. As expected, inhibitors were the most frequent treatment-related adverse event (high titer: 17 [39.5%] patients; low titer: 6 [13.9%] patients). Six of 12 patients who underwent ITI treatment in the extension phase (high titer [
n  = 5], low titer [
n  = 1]) achieved a negative inhibitor titer.

CONCLUSION:  BAY 81-8973 was effective for bleed prevention and treatment in PUPs/MTPs. The observed inhibitor rate was strongly influenced by a cluster of inhibitor cases, and consequently, slightly higher than in other PUP/MTP studies. Overall, the BAY 81-8973 benefit-risk profile remains unchanged and supported by ongoing safety surveillance. Immune tolerance can be achieved with BAY 81-8973.

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author
; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Humans, Child, Infant, Factor VIII/adverse effects, Hemophilia A/drug therapy, Treatment Outcome, Hemorrhage/chemically induced
in
Thrombosis and Haemostasis
volume
123
issue
1
pages
27 - 39
publisher
Schattauer GmbH
external identifiers
  • pmid:36626898
  • scopus:85146100208
ISSN
0340-6245
DOI
10.1055/s-0042-1757876
language
English
LU publication?
yes
additional info
The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/).
id
5e753ac2-91ce-4c49-8fe2-26d4ccd37b4e
date added to LUP
2023-01-15 19:29:25
date last changed
2024-06-09 09:47:21
@article{5e753ac2-91ce-4c49-8fe2-26d4ccd37b4e,
  abstract     = {{<p>INTRODUCTION:  BAY 81-8973, a full-length recombinant factor VIII for hemophilia A treatment, has been extensively evaluated in previously treated patients in the LEOPOLD (Long-Term Efficacy Open-Label Program in Severe Hemophilia A Disease) clinical trials.</p><p>AIM:  To assess BAY 81-8973 efficacy and safety when used for bleed prophylaxis and treatment in previously untreated/minimally treated patients (PUPs/MTPs).</p><p>METHODS:  In this phase III, multicenter, open-label, uncontrolled study, PUPs/MTPs (&lt;6 years old) with severe hemophilia A received BAY 81-8973 (15-50 IU/kg) at least once weekly as prophylaxis. Primary efficacy endpoint was the annualized bleeding rate (ABR) within 48 hours after prophylaxis infusion. Adverse events and immunogenicity were assessed. Patients who developed inhibitors were offered immune tolerance induction (ITI) treatment in an optional extension phase.</p><p>RESULTS:  Fifty-two patients were enrolled, with 43 patients (mean age: 13.6 months) treated. Median (interquartile range) ABR for all bleeds within 48 hours of prophylaxis infusion was 0.0 (0.0-1.8) among patients without inhibitors ( <br>
 n  = 20) and 0.0 (0.0-2.2) among all patients. As expected, inhibitors were the most frequent treatment-related adverse event (high titer: 17 [39.5%] patients; low titer: 6 [13.9%] patients). Six of 12 patients who underwent ITI treatment in the extension phase (high titer [ <br>
 n  = 5], low titer [ <br>
 n  = 1]) achieved a negative inhibitor titer.<br>
 </p><p>CONCLUSION:  BAY 81-8973 was effective for bleed prevention and treatment in PUPs/MTPs. The observed inhibitor rate was strongly influenced by a cluster of inhibitor cases, and consequently, slightly higher than in other PUP/MTP studies. Overall, the BAY 81-8973 benefit-risk profile remains unchanged and supported by ongoing safety surveillance. Immune tolerance can be achieved with BAY 81-8973.</p>}},
  author       = {{Ljung, Rolf and Chan, Anthony K C and Glosli, Heidi and Afonja, Olubunmi and Becker, Bastian and Tseneklidou-Stoeter, Despina and Mancuso, Maria Elisa and Saulyte-Trakymiene, Sonata and Kenet, Gili}},
  issn         = {{0340-6245}},
  keywords     = {{Humans; Child; Infant; Factor VIII/adverse effects; Hemophilia A/drug therapy; Treatment Outcome; Hemorrhage/chemically induced}},
  language     = {{eng}},
  number       = {{1}},
  pages        = {{27--39}},
  publisher    = {{Schattauer GmbH}},
  series       = {{Thrombosis and Haemostasis}},
  title        = {{BAY 81-8973 Efficacy and Safety in Previously Untreated and Minimally Treated Children with Severe Hemophilia A : The LEOPOLD Kids Trial}},
  url          = {{http://dx.doi.org/10.1055/s-0042-1757876}},
  doi          = {{10.1055/s-0042-1757876}},
  volume       = {{123}},
  year         = {{2023}},
}