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 S Powell, Uri Martinowitz, Jerzy Windyga, Giovanni Di Minno, Andrzej Hellmann, Ingrid Pabinger, Monika Maas Enriquez, Lawrence Schwartz, Jørgen Ingerslev

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)913-922
Number of pages10
JournalThrombosis and Haemostasis
Volume108
Issue number5
DOIs
StatePublished - Sep 2012

Fingerprint

Hemophilia A
Double-Blind Method
Joints
Safety
Investigational Drugs
Control Groups
Investigational Therapies
Liposomes
Sucrose
Quality of Life
Hemorrhage
Lipids
Injections
sugar formulated recombinant FVIII
Health
Therapeutics

Keywords

  • Haemophilia
  • PEGylated liposome
  • Prophylaxis
  • rFVIII-FS

ASJC Scopus subject areas

  • Hematology

Cite this

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. / Powell, Jerry S; Martinowitz, Uri; Windyga, Jerzy; Di Minno, Giovanni; Hellmann, Andrzej; Pabinger, Ingrid; Enriquez, Monika Maas; Schwartz, Lawrence; Ingerslev, Jørgen.

In: Thrombosis and Haemostasis, Vol. 108, No. 5, 09.2012, p. 913-922.

Research output: Contribution to journalArticle

Powell, Jerry S ; Martinowitz, Uri ; Windyga, Jerzy ; Di Minno, Giovanni ; Hellmann, Andrzej ; Pabinger, Ingrid ; Enriquez, Monika Maas ; Schwartz, Lawrence ; Ingerslev, Jørgen. / 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. In: Thrombosis and Haemostasis. 2012 ; Vol. 108, No. 5. pp. 913-922.
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abstract = "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.",
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