Correction, October 1, 2014: Alprolix was not the first new FIX product in 17 years. It was preceded by Baxter’s RIXUBIS [Coagulation Factor IX (Recombinant)], which was approved by the Food and Drug Administration in June 2013. This article has been updated.
Original article: Veins across the country are all breathing a figurative sigh of relief after the US Food and Drug Administration (FDA) approved Alprolix®, Coagulation Factor IX (recombinant) Fc Fusion Protein, in March 2014. This breakthrough drug is the first extended half-life factor IX (FIX) product on the market. It is expected to space infusions to weekly or every 10 days, welcome news to patients with hemophilia B.
Alprolix is indicated for the control and prevention of bleeding episodes, perioperative (surgical) management, and routine prophylaxis in adults and children with hemophilia B, factor IX deficiency. It is manufactured by Cambridge, Massachusetts-based Biogen Idec, Inc.
The goal of factor infusion is to maintain enough of the clotting protein in the bloodstream to prevent bleeding. It all comes down to half-life, the time it takes for the infused clotting factor to reach half its original concentration after being eliminated or metabolized by the body. Alprolix is manufactured using Fc fusion technology, which employs Fc receptors, proteins found in endothelial cells that line blood vessels, to bind and recycle the antibody immunoglobulin G (IgG), thereby prolonging its half-life. By fusing the FIX protein to IgG, the clotting factor is also recycled instead of being broken down, keeping it in the blood circulation longer.
Fc technology was first approved by the FDA in 1998 to treat such disorders as rheumatoid arthritis, psoriasis and chronic idiopathic thrombocytopenic purpura. It has also been used in drugs to treat Crohn’s disease, certain cancers and in transplant recipients.
Clinical trial results
B-LONG, the phase 3 clinical trial of 123 males with severe hemophilia B (less than or equal to 2% FIX level), was conducted at 50 hemophilia treatment centers in 17 countries. It compared patients in two prophylaxis regimens to those in an on-demand group. Patients were followed for up to 18 months. Results showed the half-life for Alprolix was 86.52 hours for adults in the weekly or every 10 days dosing arms. It took an average of 12 days for factor levels to drop below 1%.
Further, bleeds were controlled with one infusion in 90.4% of study participants. The annualized bleed rate was 3.0 for the weekly prophylaxis group and 1.4 for the every 10 days group vs. 17.7 for the on-demand patients. Physicians using Alprolix for the 12 participants undergoing surgery rated its ability to control bleeding as “excellent” or “good.”
For adolescents ages 12–17, the half-life was 83.59 hours. But younger children, ages 2–11, had shorter half-lives—66.40 hours for ages 2–5; 72.23 hours for ages 6–11. Because of the reduced half-life in children under 12, Biogen Idec cautions that pediatric patients will need to be monitored closely to determine the optimal dose and schedule.
The use of Alprolix in these previously treated patients with severe hemophilia B in the study did not result in the development of inhibitors, antibodies to infused factor. Headache and abnormal sensation in the mouth were the most common side effects, but occurred in few people.
Future infusion regimen
The National Hemophilia Foundation’s Medical and Scientific Advisory Council (MASAC) recommends prophylaxis, routine administration of clotting factor, for patients with severe hemophilia. Until now, the standard regimen for prophylactic factor FIX infusion was two to three times weekly.
With Alprolix, patients may be able to reduce their infusions to weekly or every 10 days. That’s a relief to overtaxed veins, and to patients, too.