Results of a phase 3 trial suggest a recombinant factor VIII Fc fusion protein (rFVIIIFc/efmoroctocog alfa, Eloctate/Elocta) can be used to prevent or reduce bleeding episodes in patients with severe hemophilia A.
Researchers found that prophylaxis with rFVIIIFc resulted in low annualized bleeding rates, and patients did not develop neutralizing antibodies.
Furthermore, the product was generally well-tolerated and had a prolonged half-life when compared with recombinant factor VIII.
Data from this study, called A-LONG, have been published in Blood.
Researchers tested rFVIIIFc in 165 male patients with severe hemophilia A who were 12 years of age and older.
Patients were divided into 3 treatment arms. Arm 1 received individualized prophylaxis, or 25 to 65 IU/kg every 3 to 5 days (n=118). Patients in arm 2 received a weekly prophylactic dose of 65 IU/kg (n=24). And patients in arm 3 received episodic treatment at doses of 10 to 50 IU/kg (n=23).
A total of 153 patients completed the study, and 757 bleeding episodes were treated with rFVIIIFc. Across the treatment arms, 87.3% of bleeding episodes were resolved with 1 injection of rFVIIIFc.
The annualized bleeding rate was significantly reduced with prophylaxis—by 92% for patients in arm 1 and 76% for those in arm 2—when compared with episodic treatment.
This was based on annualized bleeding rate estimates from a negative binomial regression model—2.91 for arm 1, 8.92 for arm 2, and 37.25 for arm 3.
The median annualized bleeding rates were 1.6 in arm 1, 3.6 in arm 2, and 33.6 in arm 3.
In arm 3, there were 9 patients who received rFVIIIFc to control bleeding during major surgery. In these cases, physicians rated the hemostatic response as “excellent” (n=8) or “good” (n=1).
There were no serious adverse events related to rFVIIIFc, and none of the patients developed neutralizing antibodies.
The most common adverse events (with an incidence of 5% or more) that occurred outside the perioperative period included nasopharyngitis, arthralgia, headache, and upper respiratory infection.
The researchers also compared the pharmacokinetics of rFVIIIFc and recombinant factor VIII. And they found the terminal half-life of rFVIIIFc was extended 1.5-fold compared to recombinant factor VIII—19.0 hours and 12.4 hours, respectively.
rFVIIIFc was developed using Fc fusion technology, which takes advantage of a naturally occurring pathway that delays the breakdown of IgG1 protein in the body by recycling it back into the bloodstream. This technology prolongs the time rFVIIIFc circulates in the body.
“There is an unmet medical need in the hemophilia community for longer intervals between prophylactic infusions while maintaining good control of bleeding episodes,” said study author Johnny Mahlangu, MD, director of the Haemophilia Comprehensive Care Centre at the University of the Witwatersrand and National Health Laboratory Service in Johannesburg, South Africa.
“A-LONG is the first clinical study to show that effective control over breakthrough bleeding may be achieved with once- or twice-weekly prophylactic infusions in people with severe hemophilia A.”
This study was funded by Biogen Idec, makers of rFVIIIFc.
