The US Food and Drug Administration (FDA) has approved antihemophilic factor (recombinant), single chain (rVIII-single chain; Afstyla, CSL Behring) for on-demand treatment and control of bleeding episodes, routine prophylaxis to decrease the frequency of bleeding episodes, and perioperative management of bleeding in children and adults with hemophilia A (congenital factor VIII deficiency).
Once activated, rVIII-single chain is identical to natural factor VIII, the company said in a news release.
This approval is the sixth FDA approval of hemophilia A in the United States in the last 2 years.
"FDA's approval of the first recombinant single-chain therapy that offers long-lasting hemostatic efficacy provides an important new treatment option for patients and healthcare providers as it has been specifically designed for increased molecular stability and duration of action," Lisa Boggio, MD, assistant professor of internal medicine, hematology and oncology, and clinical director of the Rush Hemophilia and Thrombophilia Center, Rush University Medical Center, Chicago, Illinois, explained in the news release.
Dr Boggio served as a clinical development program study investigator for An Open-label Safety, Efficacy and Pharmacokinetic Study of a Recombinant FVIII Compared to Recombinant Human Antihemophilic FVIII in Patients With Severe Hemophilia A (AFFINITY).
"[Afstyla] offers patients an opportunity for excellent efficacy with a strong safety profile and twice-weekly dosing — potentially helping patients to fit treatment into their active lives," she said.
The treatment is intended for intravenous dosing two to three times per week.
The FDA's decision follows a review of data from the AFFINITY clinical development program, which included two pivotal trials and one extension open-label multicenter trial that studied the drug's safety and efficacy in children, adolescents, and adults with hemophilia A.
The trials demonstrated a median annualized spontaneous bleeding rate of 0.00 in the adult, adolescent, and pediatric studies. When administered prophylactically, the median annualized bleeding rate was 1.14 in adults and adolescents and 3.69 in children younger than 12 years.
A total of 1195 bleeds were treated during the pivotal trial (848 in adults and adolescents; 347 in children). Of those, no more than two infusions of rVIII-single chain were required to effectively control 94% of bleeding events in adults and adolescents and 96% of bleeds in children. One infusion alone was enough to effectively control 81% of bleeding events in adults and adolescents and 86% of bleeds in children.
Thirteen adult or adolescent patients underwent a total of 16 surgeries; of those, hemostatic efficacy of rVIII single-chain was rated as excellent in 15 surgeries and good in one surgery.
The most frequent adverse events (>0.5%) in the clinical studies were dizziness and hypersensitivity.
rVIII single-chain is contraindicated for patients with von Willebrand disease and those who have had life-threatening hypersensitivity reactions to the drug or its excipients or to hamster proteins. rVIII single-chain can be given by the patient or a caregiver after training and with the approval of a healthcare provider or hemophilia treatment center. Some patients younger than 12 years may require a higher dose per kilogram body weight and/or more frequent administration.
Patients may experience hypersensitivity reactions, including anaphylaxis, and should be advised to report hypersensitivity symptoms immediately.
Hemophilia A is a congenital bleeding disorder that mainly affects males as a result of deficient or defective factor VIII. Patients with the disorder can suffer from prolonged or spontaneous bleeding that can occur in the muscles, joints, or internal organs. Approximately 1 in every 6000 males are born with the disorder.
Afstyla is expected to be available early this summer.
FDA Approves Afstyla for Adults, Children With Hemophilia A. Medscape. May 26, 2016.May 27, 2016.