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CC BY 4.0 · Thromb Haemost 2023; 123(01): 027-039
DOI: 10.1055/s-0042-1757876
Coagulation and Fibrinolysis

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

Rolf Ljung
1   Department of Clinical Sciences Lund-Pediatrics, Lund University, Lund, Sweden
,
Anthony K. C. Chan
2   McMaster Children's Hospital, McMaster University, Hamilton, Ontario, Canada
,
Heidi Glosli
3   Centre for Rare Disorders and Department of Pediatric Research, Oslo University Hospital, Oslo, Norway
,
Olubunmi Afonja
4   Bayer, Whippany, New Jersey, United States
,
Bastian Becker
5   Bayer, Wuppertal, Germany
,
Despina Tseneklidou-Stoeter
6   Bayer, Berlin, Germany
,
Maria Elisa Mancuso 
7   Center for Thrombosis and Hemorrhagic Diseases, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy
,
Sonata Saulyte-Trakymiene
8   Clinic of Children's Diseases, Faculty of Medicine, Vilnius University Hospital Santaros Klinikos, Vilnius University, Vilnius, Lithuania
,
Gili Kenet
9   Sheba Medical Center, The Israeli National Hemophilia Center, The Amalia Biron Thrombosis Research Institute and The Sackler Medical School, Tel Aviv University, Tel-Hashomer, Israel
› Author Affiliations Funding This study was funded by Bayer. Medical writing assistance was provided by Julie Smith of Julie Smith Medical Writing (Toronto, Canada) and was fully funded by Bayer.
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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 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.

Keywords

immune tolerance induction - clinical trial - factor VIII - hemophilia A - inhibitors - prophylaxis

Supplementary Material



Publication History

Received: 08 March 2022

Accepted: 30 August 2022

Article published online:
10 January 2023

© 2023. 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/)

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