The US Food and Drug Administration (US FDA) has approved Biogen Idec's Alprolix Coagulation Factor IX (Recombinant), Fc Fusion Protein, the first recombinant, DNA derived haemophilia B therapy with prolonged circulation in the body.

Alprolix is indicated for the control and prevention of bleeding episodes, perioperative (surgical) management and routine prophylaxis in adults and children with haemophilia B. The therapy is shown to reduce bleeding episodes with prophylactic (protective) infusions starting at least a week apart.

The approval of Alprolix is the first significant advance in haemophilia B treatment in more than 17 years. The therapy is clinically proven to reduce bleeding episodes with a favourable safety and tolerability profile. It is developed using a process called Fc fusion and is the first haemophilia therapy to demonstrate prolonged circulation in the body, which has been shown in adults and adolescents with haemophilia to extend the time between prophylactic infusions.

“The FDA approval of Alprolix is a significant milestone for the haemophilia B community, and represents an important first step in our commitment to transform the care of people with haemophilia,” said George A. Scangos,, chief executive officer of Biogen Idec. “Alprolix offers people with haemophilia B the ability to prevent or reduce bleeding episodes with prophylactic infusions starting at least a week apart. We believe this new therapy will help more people with haemophilia and their caregivers realise the benefits of this treatment approach.”

The National Hemophilia Foundation (NHF) recommends routine prophylaxis as optimal for the treatment of people with severe haemophilia. Studies show people with severe haemophilia who follow this type of regimen experience fewer bleeding episodes and their related risks. Complications of bleeding episodes may range from severe swelling and pain to arthritis, joint damage and physical disability.

“Paedophilia has a significant impact on people whom it affects, throughout their lives,” said Patrick F. Fogarty, managing director, 4 assistant professor of medicine at the Hospital of the University of Pennsylvania, and director, Penn Comprehensive Hemophilia and Thrombosis Programme. “Alprolix addresses a critical need by allowing people with haemophilia B to maintain factor levels with prophylactic infusions once weekly or once every 10 days. We hope this will facilitate use of prophylactic therapy.”

Haemophilia B is a rare, chronic, inherited disorder in which the ability of a person’s blood to clot is impaired, which can lead to recurrent and extended bleeding episodes. Therapies for haemophilia B can be administered either on a schedule to help prevent or reduce bleeding episodes (prophylaxis), or to help control a bleeding episode when it occurs (on-demand). According to NHF guidelines, traditional haemophilia B therapy requires prophylactic infusions two or more times a week.

“The haemophilia community is excited about new therapy options for the prophylactic management of haemophilia B,” said Val Bias, chief executive officer of the National Hemophilia Foundation. “This approval is a significant step forward because it provides an important new option and expanded choice for the haemophilia B community.”

The approval of Alprolix is based on results from the global, Phase 3 B-LONG study, as well as interim pharmacokinetic (measurement of the presence of the therapy in a person’s body over time) and safety data from the Phase 3 Kids B-LONG study. B-LONG study results showed that adults and adolescents with severe haemophilia B achieved prevention or reduction of bleeding episodes with prophylactic infusions at least a week apart.

The study included two prophylaxis regimens – the weekly prophylaxis arm and the individualised-interval prophylaxis arm, in which the dosing interval started at once every 10 days. The overall median dosing interval with individualized-interval prophylaxis was 12.5 days; during the last six months of the study, the median interval was 13.8 days. More than 90 per cent of all bleeding episodes were controlled by a single Alprolix infusion.

No participants in the B-LONG study developed inhibitors (neutralising antibodies that may interfere with the activity of the therapy) to Alprolix. There were no reports of vascular clots or serious allergic reactions. Across the routine prophylaxis and on-demand therapy arms, adverse reactions were reported in 8.4 percent of participants. These adverse reactions included headache, oral paresthesia (abnormal sensation in the mouth), dizziness, dysgeusia (taste alteration), breath odour, fatigue, infusion site pain, palpitations, obstructive uropathy (an obstructing clot in the urinary collecting system) and hypo-tension (low blood pressure). Each event occurred in two or fewer study participants.

An interim analysis from an ongoing, multi-centre phase 3 paediatric study – Kids B-LONG –showed no inhibitors were detected, and the increase in half-life (a measure of the time therapy remains in the body) seen with Alprolix was consistent with data reported in adults and adolescents.

Alprolix was recently approved by Health Canada for the treatment of haemophilia B and is currently under review by regulatory authorities in several other countries, including Australia and Japan.

Biogen Idec plans to make Alprolix commercially available to people with haemophilia B in the United States in early May. To help address the haemophilia B community’s needs, Biogen Idec is committed to providing equitable access to therapy, as well as a variety of personalised assistance and resources through MyAlprolix Services.

B-LONG was a global, open-label, multi-centre Phase 3 study that evaluated the efficacy, safety and pharmacokinetics of Alprolix in 123 males aged 12 years and older with haemophilia B. The study involved 50 haemophilia treatment centres in 17 countries on six continents.

The overall median annualisd bleeding rates (ABR), or projected rate of bleeding episodes per year, reported in the study were 3.0 for the weekly prophylaxis arm, 1.4 for the individualised-interval prophylaxis arm and 17.7 for the on-demand treatment arm. For 12 study participants undergoing 14 major surgical procedures, treating physicians rated the ability of Alprolix to control bleeding as “excellent” or “good” in 100 per cent of these surgeries.

Common adverse reactions (incidence of greater than or equal to 1 percent) from the B-LONG study were headache and oral paresthesia (an abnormal sensation in the mouth).

Alprolix Coagulation Factor IX (Recombinant), Fc Fusion Protein] is the first recombinant, clotting factor therapy with prolonged circulation in the body. It is indicated for the control and prevention of bleeding episodes, perioperative (surgical) management and routine prophylaxis in adults and children with haemophilia B. Alprolix is not indicated for immune tolerance induction therapy, which is a treatment for people with inhibitors, and should not be used in individuals with a known history of serious allergic reactions. Alprolix was developed by fusing factor IX to the Fc portion of immunoglobulin G subclass 1, or IgG1 (a protein commonly found in the body). It is believed that this enables Alprolix to use a naturally occurring pathway to prolong the time the therapy remains in the body. While Fc fusion has been used for more than 15 years, Biogen Idec is the only company to apply it in haemophilia.

Haemophilia B occurs in about one in 25,000 male births annually, and more rarely in females, affecting about 4,000 people in the United States. The World Federation of Hemophilia global survey conducted in 2012 estimates that approximately 28,000 people are currently diagnosed with haemophilia B worldwide. It is caused by having substantially reduced or no factor IX activity, which is needed for normal blood clotting. People with haemophilia B experience bleeding episodes that cause pain, irreversible joint damage and life-threatening haemorrhages. Prophylactic infusions of factor IX temporarily replace clotting factors necessary to control bleeding and prevent new bleeding episodes.
About the Biogen Idec and Sobi Collaboration

Biogen Idec and Swedish Orphan Biovitrum (Sobi) are partners in the development and commercialisation of Alprolix for haemophilia B. Biogen Idec leads development, has manufacturing rights, and has commercialisation rights in North America and all other regions in the world excluding the Sobi territory. Sobi has the right to opt in to assume final development and commercialisation in Europe, Russia, the Middle East and Northern Africa.