Voncento Safe, Effective in Young Children With Hemophilia A, Trial Finds
Voncento — a highly concentrated mixture of Von Willebrand factor (VWF) and clotting factor VIII (FVIII) — was seen to safely and effectively treat or prevent bleeds in children, age 12 and younger, with severe hemophilia A, according to data from a Phase 3 trial.
Findings were reported in the study “Efficacy, safety and pharmacokinetic results of a phase III, open-label, multicenter study with a plasma-derived von Willebrand factor (VWF)/factor VIII (FVIII) concentrate in pediatric patients <12 years of age with hemophilia A (SWIFTLY-HA study),” published in the Journal of Blood Medicine.
Voncento, developed by CSL Behring (marketed as Biostate or Aleviate in some countries), is a replacement therapy that supplies FVIII — the blood clotting protein that is missing or is defective in hemophilia A patients. The medication also contains VWF, another clotting factor. Both are derived from human plasma — the clear, liquid part of blood.
Across the European Union, the Voncento is approved to treat and prevent bleeding episodes in people with hemophilia A starting at age 12, as well as adults and adolescents (12 and above) with Von Willebrand disease when another medicine called desmopressin is ineffective or cannot be given.
In the U.S., Voncento is approved to treat Von Willebrand disease in adults.
An open-label Phase 3 clinical trial, called SWIFTLY-HA (NCT01229007), was carried out at sites in Europe and Latin America to test its safety and efficacy in young children with severe hemophilia A. (In open-label studies all are given the investigative treatment; there’s no placebo group as a comparative study arm.)
Voncento was given as an intravenous infusion in the trial “either on-demand, to treat bleeding episodes as they arose, or prophylactic at regular intervals, with the aim of preventing bleeding,” the researchers wrote.
The study included 35 children, with a median age of 6 (range, infants through 11 years old). Of these, 17 received on-demand treatment and 18 were given Voncento as a preventive treatment every two to three days. Those using on-demand treatment were a median of 3.5 years younger than the preventive treatment group.
All children previously had at least 20 days of exposure to a FVIII replacement therapy, and remained in the study for a median of 300 days (almost one year). Most, 28 children or 80%, completed the study.
Voncento’s efficacy in stopping or preventing bleeds, one of numerous primary trial goals, was measured using a grading scale. Children receiving on-demand treatment reported a total of 318 bleeding episodes that required Voncento’s use, and those on preventive treatment reported 172 episodes.
For on-demand treatment, investigators rated its efficacy as excellent in 24% of all bleeding episodes (77 out of the 318) and good in 76% of them (241 out of 318).
As a prophylaxis (preventive) treatment, Voncento’s effectiveness was rated as excellent for 86% of all bleeding episodes (148 out of 172), and good in 13% (23 out of 172). Most of these bleeds (92%) were successfully controlled with one infusion.
Trial results also showed that Voncento had a similar pharmacokinetic profile — a drug’s movement through and out of the body — in children up to age 5 as in those ages 6 to 12. It cleared the younger group slightly faster than it did for the older group.
Five children underwent surgery during the study. Voncento’s efficacy in controlling bleeding was rated by investigators as excellent in two of the surgeries, and as good for the other three. Blood loss during surgery was lesser or comparable to what would be expected in someone without a bleeding disorder.
Among on-demand group children, 33 side effects were reported in 11 (65%) of them during treatment, and 64 side effects were reported involving 12 (67%) children in the prophylaxis group. Voncento was “well-tolerated,” the researchers reported, with most frequent side effects being cough, fever, inflammation of the mucus membrane of the nose (rhinitis), and rash.
Three children had FVIII inhibitors, or neutralizing antibodies against FVIII. These inhibitors were temporary in two cases and persisted in one. No other safety concerns were noted.
“Overall, these results demonstrate a favorable benefit-risk profile for [Voncento], and support its use to treat bleeding events in children with hemophilia A,” the researchers concluded.
Two of the study’s eight scientists are employees of CSL Behring.