Thromb Haemost 2012; 108(05): 913-922
DOI: 10.1160/TH12-03-0188
Blood Coagulation, Fibrinolysis and Cellular Haemostasis
Schattauer GmbH

Efficacy and safety of prophylaxis with once-weekly BAY 79–4980 compared with thrice-weekly rFVIII-FS in haemophilia A patients

A randomised, active-controlled, double-blind study
Jerry Powell*
1   Division of Hematology/Oncology, School of Medicine, University of California at Davis, Davis, California, USA
,
Uri Martinowitz
2   The National Hemophilia Center, Sheba Medical Center, Tel Hashomer, Israel
,
Jerzy Windyga
3   Department of Disorders of Haemostasis and Internal Medicine, Institute of Haematology and Transfusion Medicine, Warsaw, Poland
,
Giovanni Di Minno
4   Regional Reference Centre for Coagulation Disorders, Department of Clinical and Experimental Medicine, Federico II University Hospital, Naples, Italy
,
Andrzej Hellmann
5   Department of Hematology, Medical University of Gdansk/Poland
,
Ingrid Pabinger
6   Clinical Division of Haematology and Haemostaseology, Department of Medicine I, Medical University Vienna, Austria
,
Monika Maas Enriquez
7   Bayer Pharma AG, Wuppertal, Germany
,
Lawrence Schwartz
8   Bayer HealthCare Pharmaceuticals Inc., Montville, New Jersey, USA
,
Jørgen Ingerslev*
9   Center for Haemophilia and Thrombosis, Aarthus University Hospital, Skejby, Denmark
,
the LipLong Study Investigators › Author Affiliations
Financial support: This study was sponsored and funded by Bayer HealthCare.
Further Information

Publication History

Received: 27 March 2012

Accepted after major revision: 22 August 2012

Publication Date:
29 November 2017 (online)

Summary

The benefits of prophylaxis of haemophilia A patients regarding joint health and quality-of-life are well established. However, adherence to an up to every-other-day infusion regimen is a barrier to widespread adoption of prophylaxis. BAY 79–4980 is an investigational drug consisting of rFVIII-FS (sucrose-formulated recombinant FVIII) reconstituted with liposome solvent. Previous clinical studies showed extended protection from bleeding after a single injection of BAY 79–4980 (13.3 ± 6.2 days) compared with rFVIII-FS (7.2 ± 1.7 days). The effect of once-a-week prophylaxis with BAY 79–4980 (35 IU/kg) compared with three times-per-week rFVIII-FS (25 IU/kg) in previously treated, severe haemophilia A patients was evaluated in a 52-week, double-blind, two-arm, randomised, controlled study. The primary and secondary endpoints were protection from total bleeds and joint bleeds, respectively. Short- and long-term safety and tolerability of BAY 79–4980 including effects on lipid levels were assessed. A total of 139 and 131 subjects were evaluable for safety and efficacy analyses, respectively. A large difference in efficacy between treatment groups was observed with 72.1% (49/68) in the rFVIII-FS control group demonstrating <9 bleeds/year compared with 38.1% (24/63) of BAY 79–4980-treated subjects. A similar difference was seen in annualised joint bleeds, with 43 subjects (63.2%) in the control group demonstrating <5 joint bleeds/year compared with 24 subjects (38.1%) treated with BAY 79–4980. The distribution of bleeds seven days post-prophylactic treatment with BAY 79–4980 showed that 61% of bleeds occurred after day 4 post dosing. There were no safety concerns identified. The investigational treatment arm was prematurely discontinued due to failure to achieve the primary endpoint.

* Coordinating Investigators.


# See Appendix for full list of investigators and affiliations.