Biogen Idec and Swedish Orphan Biovitrum AB recently announced the publication of results from a Phase 3 study of ALPROLIX™, the companies’ investigational long-lasting recombinant factor IX Fc fusion protein therapy for hemophilia B. The study, “Phase 3 Study of Recombinant Factor IX Fc Fusion Protein in Hemophilia B,” was published in the December 12, 2013, issue of The New England Journal of Medicine. The lead author of the study was Jerry S. Powell, MD, University of California at Davis.
B-LONG is a global, multi-center study that evaluated the efficacy, safety and pharmacokinetics (measurement of the presence of the drug in a patient’s body over time) of ALPROLIX in 123 males with hemophilia who were 12 years and older. The study involved 50 hemophilia treatment centers in 17 countries.
B-LONG evaluated ALPROLIX™ via four treatment regimens: weekly prophylaxis (arm 1); individualized-interval prophylaxis dosing, starting at every 10 days (arm 2); episodic (on-demand) therapy as needed to manage bleeding episodes (arm 3); perioperative (surgical) management (arm 4). Dose (arm 1) and interval (arm 2) were adjusted during the study to maintain target factor IX levels intended to prevent bleeding.
The overall median annualized bleeding rates (ABR), the number of bleeds yearly, were 3.0 for weekly prophylaxis arm and 1.4 for individualized-interval prophylactic regimens, compared to 17.7 for the episodic therapy group. The median dosing interval with individualized-interval prophylaxis (arm 2) was 12.5 days. Bleeding episodes for participants in arms 1-3 were documented and more than 90% of all bleeding episodes were controlled by a single infusion of ALPROLIX™. The product was assessed in the perioperative management of 12 study participants undergoing 14 major surgical procedures. The treating physicians rated response to surgery of ALPROLIX™ as “excellent” or “good” in 100% of these surgeries.
“Today, many people with hemophilia B do not follow a prophylactic regimen, and the burdensome infusion schedules associated with currently available treatment may contribute to its limited adoption,” said Marilyn Manco-Johnson, MD, professor of Pediatrics, University of Colorado and director, Hemophilia and Thrombosis Center, University of Colorado and Children’s Hospital, Colorado. “The National Hemophilia Foundation recommends a prophylactic regimen as optimal for people with severe hemophilia, and studies show this approach reduces bleeding episodes and associated risks. It is my hope that long-lasting therapies in development, such as ALPROLIX™, may lessen the burden of prophylactic dosing for people with hemophilia B, and encourage adoption.”
Fc Fusion Studies in Children
The two companies also announced results from Phase 3 studies of ALPROLIX™ and ELOCTATE™, an investigational long-lasting recombinant factor VIII Fc fusion protein product for hemophilia A, which included an interim analysis of pediatric pharmacokinetics (PK) data. These interim data demonstrate that ALPROLIX™ and ELOCTATE™ have consistently prolonged half-lives (a measure of the time therapy circulates in the bloodstream) in children, compared to study participants’ prior therapies. These results were consistent with PK results in adults and adolescents. The interim findings were presented at the 55th Annual Meeting of the American Society of Hematology on December 7-10, 2013, in New Orleans, LA.
“As seen in adult studies, interim data demonstrated that in children, the use of Fc fusion technology prolongs the half-lives of these experimental therapies,” said Guy Young, MD, director, Hemostasis and Thrombosis Center, Children’s Hospital Los Angeles. “We are investigating whether prophylactic dosing intervals longer than the currently available therapy are possible with these treatments. The frequency of traditional prophylactic regimens is a significant challenge for parents of children with hemophilia, many of whom require infusions multiple times per week.”
Final results of the pediatric studies, which will be presented at a future meeting, will evaluate the safety and efficacy of ALPROLIX™ and ELOCTATE™, as well as provide further PK information.
Source: Biogen Idec press releases dated December 4 and December 9, 2013