There are times when less really is more. With the June 6, 2014, US Food and Drug Administration (FDA) approval of ELOCTATE® [Antihemophilic Factor (Recombinant), Fc Fusion Protein], patients with hemophilia A can potentially infuse less often, gaining more sleep, more time and more peace of mind. ELOCTATE is the first recombinant therapy for people with hemophilia A [factor VIII (FVIII) deficiency] with elongated circulation in the blood, according to manufacturer Biogen Idec, Inc., based in Cambridge, Massachusetts. This announcement comes on the heels of FDA approval in March 2014 of Alprolix, Biogen’s prolonged half-life FIX product. (See “Durable Drug,” HemAware Summer 2014.) ELOCTATE is indicated for the control and prevention of bleeding episodes, perioperative (surgical) management, and routine prophylaxis in adults and children with hemophilia A.
Routine prophylactic infusion of clotting factor helps patients maintain enough clotting protein in the bloodstream to prevent bleeding. The National Hemophilia Foundation’s Medical and Scientific Advisory Council (MASAC) recommends prophylaxis, routine administration of clotting factor, for patients with severe hemophilia. The typical prophylaxis schedule for patients with hemophilia A entails infusing factor product three times weekly, up to every other day. But veins wear out, sleep is precious and extra time in the morning is hard to find.
To remedy this routine, drug manufacturers are testing ways to create prolonged half-life factor products. One method is to extend the half-life, the time it takes for the infused clotting factor to reach half its original concentration after being metabolized or eliminated, by piggybacking a drug onto one of the body’s proteins. ELOCTATE uses Fc fusion technology to accomplish this. Fc receptors in endothelial cells lining blood vessels bind and recycle the antibody immunoglobulin G (IgG), prolonging its half-life. By fusing the FVIII protein to a recombinant version of the Fc region of IgG, the clotting factor is also recycled, staying in the circulation longer. Fc fusion technology was first approved by the FDA in 1998 to treat rheumatoid arthritis, psoriasis and other disorders.
Clinical trial results
The Phase 3 A-LONG clinical trial was conducted at multiple centers around the world on 165 study subjects with severe hemophilia A who were at least 12 years old and had been previously treated. Patients were placed in three groups: individualized prophylaxis, weekly prophylaxis or on-demand dosing. Results showed that nearly ¹/³ of people in the first group who were treated for six months or longer were able to stretch their infusion interval to five days by the last three months of the trial period. The average half-life of ELOCTATE was 19.7 hours for adults and 16.4 hours for adolescents 12–17 years old. Further, 98% of bleeds were controlled with one or two ELOCTATE infusions.
For the 71 boys enrolled in the Phase 3 Kids A-LONG study, the average half-life of ELOCTATE was 14.6 hours for 6- to 11-year-olds and 12 hours for those ages 2–5. Because clearance of the drug is significantly higher in children, Biogen said dosing will be more frequent in younger children.
Overall adverse effects were minor. No inhibitors (antibodies to infused factor) were reported, and a handful of patients experienced joint pain and malaise.
For patients on ELOCTATE, the prophylaxis schedule may be stretched at home to every four days, or even once a week, depending on the patient. That means fewer hectic mornings and more time for other pursuits.