Yonsei Med J.  2015 Jul;56(4):935-943. 10.3349/ymj.2015.56.4.935.

Efficacy, Safety, and Pharmacokinetics of Beroctocog Alfa in Patients Previously Treated for Hemophilia A

• Hyun SY
• Park SY
• Lee SY
• Kook H
• Paik SH
• Jang IJ
• Lee KS

• KMID: 2366332
• DOI: http://doi.org/10.3349/ymj.2015.56.4.935

Abstract

PURPOSE
Beroctocog alfa is a second generation recombinant factor VIII manufactured by removing the B-domain from factor VIII. This prospective clinical trial was conducted to evaluate the efficacy, safety, and pharmacokinetics of beroctocog alfa in patients of ages > or =12 years previously treated for severe hemophilia A.
MATERIALS AND METHODS
Seventy subjects received beroctocog alfa as an on-demand treatment for acute hemorrhage.
RESULTS
The final hemostatic effect was excellent in 35 subjects (50%) and good in 26 subjects (37.1%). The drug showed an overall efficacy rate of 87.1%. The majority of acute hemorrhages was treated by administering the study drug once (86.2%) or twice (10.0%), and the mean dose administered per single infusion was 28.55+/-6.53 IU/kg. Ten subjects underwent 12 surgical procedures, and hemostatic efficacy was excellent in seven cases (58.3%) and good in five cases (41.7%), showing a 100% efficacy rate. A total of 52 of 88 subjects (59.0%) experienced 168 adverse events. There were 18 serious adverse events (10.7%) in 11 subjects, and two (mild dyspnea and facial edema) in one subject were related to the study drug. Only one subject formed a de novo factor VIII inhibitor, for an occurrence rate of 1.4% (one-sided 95% upper confidence limit: 3.85%). The final elimination half-life was 13.3 h and 12.6 h at baseline and 6 months after administration, respectively.
CONCLUSION
Our results suggest that beroctocog alfa is safe and efficacious as either an on-demand treatment for acute hemorrhage or a surgical prophylaxis in patients with hemophilia A.

Keyword

Hemophilia A; factor VIII; B-domain-deleted factor VIII

MeSH Terms

Adult
Consumer Product Safety
Dyspnea
Factor VIII/adverse effects/*pharmacokinetics/therapeutic use
Female
Hemophilia A/*drug therapy
Hemorrhage/prevention & control
Hemostasis
Hemostasis, Surgical/methods
Humans
Male
Middle Aged
Prospective Studies
Recombinant Proteins/adverse effects/*pharmacokinetics/*therapeutic use
Treatment Outcome
Factor VIII
Recombinant Proteins

Figure

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  Fig. 1 Status of subjects who participated in the acute hemorrhage treatmnt study (study 1). ITT, intention-to-treat; PP1, per-protocol 1; PP2, per-protocol 2; FVIII, factor VIII.

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  Fig. 2 SDS-PAGE to evaluate the homogeneity of beroctocog alfa and other recombinant factor VIII (rFVIII) products. Lane #M: molecular weight standard (Biorad), lane #1: berotocog alfa, lane #2: commercial B domain deleted rFVIII, lane #3: commercial full length rFVIII. SDS-PAGE, sodium dodecyl sulphate-polyacrylamide gel electrophoresis.

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