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Long-Acting Factor VIII for Hemophilia A

Summary and Comment |
November 19, 2013

Long-Acting Factor VIII for Hemophilia A

  1. David Green, MD, PhD

Recombinant factor VIIIFc fusion protein with prolonged half-life reduced bleeding rates in patients with severe hemophilia A, but cost is a factor.

  1. David Green, MD, PhD

In patients with severe hemophilia A (factor VIII deficiency), bleeding can be prevented by prophylaxis with factor VIII concentrates. However, because the clotting factor has a short half-life, infusions must be given at least 3 to 4 times per week.

To evaluate the safety and efficacy of the novel recombinant factor VIII Fc fusion protein (rFVIIIFc) to reduce the frequency of prophylactic injections, investigators conducted a manufacturer-sponsored, phase III, partially randomized trial involving 165 males (age, ≥12) with severe hemophilia A. Pharmacokinetic data from 28 patients confirmed that the half-life of rFVIIIFc was significantly longer than that of rFVIII (19.0 vs. 12.4 hours; P<0.001) and that it positively correlated with the level of von Willebrand factor (r=0.67; P<0.001).

Results were as follows:

  • For the 115 patients switched from prophylaxis or episodic treatment with standard FVIII to individualized rFVIIIFc every 3 to 5 days (mean weekly dose, 85.4 IU/kg), the annualized bleeding rate (ABR) was 2.9; 45% experienced no bleeding.

  • For the 24 patients switched from episodic treatment with standard FVIII to weekly rFVIIIFc (mean dose, 65.8 IU/kg), the ABR was 8.9; 17% experienced no bleeding.

  • For the 23 patients who previously received episodic treatment with standard FVIII and continued it with rFVIIIFc, the ABR was 37.3.

  • Adverse events were infrequent overall, and no patients developed thrombosis, serious hypersensitivity, or inhibitors.

Comment

This preparation of recombinant factor VIII allowed a decrease in the dosing frequency for the majority of patients with severe hemophilia A. It also was effective in preventing spontaneous hemorrhages and surgical bleeding, and it had minimal side effects. However, relatively large doses of the product were required to decrease the number of bleeding episodes (e.g., a mean weekly dose of 85 U/kg in the group infusing every 3 to 5 days). This calculates to a yearly dose of more than 300,000 U in a 70 kg man. Because the price for all current recombinant factor VIII products exceeds $1.00 per U, and the price of this long-acting factor VIII is likely to be even higher, using this product might be financially prohibitive for most hemophiliacs.

  • Disclosures for David Green, MD, PhD at time of publication Consultant / Advisory board Altor Bioscience Grant / research support NIH

Citation(s):

Reader Comments (1)

ZWI ZUR Physician, Hematology

Why the ABRs written here are different from those that are written in the abstract ?
Quote:
"Median ABRs observed in arms 1, 2, and 3 were 1.6, 3.6, and 33.6, respectively. "

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