The US Food and Drug Administration (US FDA) has approved Biogen Idec's Eloctate [Antihemophilic Factor (Recombinant), Fc Fusion Protein] for the control and prevention of bleeding episodes, perioperative (surgical) management and routine prophylaxis in adults and children with haemophilia A.

Eloctate is the first recombinant haemophilia A therapy with prolonged circulation in the body. It is the only treatment for haemophilia A to reduce the frequency of bleeding episodes with prophylactic infusions every three to five days, offering people with haemophilia A the potential to extend the interval between prophylactic infusions.

“The proven ability of Eloctate to provide protection from bleeding episodes with prolonged circulation marks the first significant haemophilia A treatment advance in more than 20 years,” said George A. Scangos, chief executive officer of Biogen Idec. “As a company deeply committed to improving the lives of people with haemophilia, we are excited to bring this important innovation to those living with haemophilia A.”

The recommended starting prophylactic regimen for Eloctate is 50 IU/kg every four days. Based on clinical response, the regimen may be adjusted in the range of 25 to 65 IU/kg and every three to five days.

In clinical trials, Eloctate was effective for both routine prophylaxis and to treat acute bleeding episodes with a favourable safety and tolerability profile. It was developed using a process called Fc fusion, which is designed to prolong the therapy’s circulation in the body using a natural pathway. The FDA’s approval is the first regulatory approval worldwide for Eloctate, and the therapy is currently under review by regulatory authorities in several other countries, including Canada, Australia and Japan. This FDA action follows regulatory approvals of Biogen Idec’s haemophilia B therapy, alprolix [Coagulation Factor IX (Recombinant), Fc Fusion Protein], in the United States, Canada and Australia.

Haemophilia A is a rare, chronic, genetic disorder in which the ability of a person’s blood to clot is impaired. This can lead to recurrent and extended bleeding episodes. Complications of bleeding episodes may range from severe swelling and pain to arthritis, joint damage, physical disability and death. According to the National Haemophilia Foundation (NHF) guidelines, traditional haemophilia A prophylactic therapy involves infusions three times per week or every other day, which equates to approximately 150 to 180 infusions per year.

“Prophylactic treatment is recommended for people with severe haemophilia, and following a protective regimen can be burdensome given the frequency of infusions required,” said Patrick F. Fogarty, M.D., assistant professor of medicine at the Hospital of the University of Pennsylvania, and director, Penn Comprehensive Haemophilia and Thrombosis Programme. “Infusion frequency is a major challenge for people with haemophilia, and I believe Eloctate begins to address this burden while protecting against bleeding episodes.”

Therapies for haemophilia A, the most common form of haemophilia, can be administered either on a schedule to help prevent or reduce bleeding episodes (prophylaxis), or to control bleeding when it occurs (on-demand). The NHF recommends routine prophylaxis as optimal for the treatment of people with severe haemophilia. In recent years, regimens have shifted from on-demand treatment to routine prophylaxis because of observed improvement in long-term clinical outcomes, such as joint damage.

“We are encouraged by the arrival of new and innovative therapies, which may help address treatment gaps for the approximately 16,000 adults and children living with haemophilia A in the United States,” said Val Bias, chief executive officer of the NHF. “These advances, in conjunction with continued community education and empowerment, are critical to effectively serving the needs of people with the disorder.”

The approval of Eloctate is based on results from the global, phase 3 A-LONG clinical study, as well as interim pharmacokinetic, or PK, and safety data from the phase 3 Kids A-LONG study. PK is the measurement of the presence of the therapy in a person’s body over time.

The A-LONG study was an open-label, multi-center study that examined the efficacy, safety and PK of Eloctate in 165 previously treated males 12 years of age and older with severe haemophilia A. Results showed that adults and adolescents with severe haemophilia A achieved a statistically significant reduction of bleeding episodes in both of the study’s prophylaxis arms, relative to the on-demand treatment arm. In addition, 98 per cent of bleeding episodes were controlled with one or two Eloctate infusions.

The study evaluated individualised and weekly prophylaxis to reduce or prevent bleeding episodes, and on-demand dosing to treat bleeding episodes. In the individualised arm, each study participant started on a twice-weekly dosing regimen. Participants’ PK parameters were used to guide adjustments to dosing interval (every three to five days), and dose (25 to 65 IU/kg) to target a minimum factor VIII level of 1 to 3 IU/dL or higher as needed to maintain control of breakthrough bleeding episodes. In the study, the dose in the weekly prophylaxis arm was 65 IU/ kg/week. The overall median annualised bleeding rates (ABR), or projected number of bleeding episodes per year, reported in the study were for the individualised prophylaxis arm, for the weekly prophylaxis arm and 33.6 for the on-demand arm.

No participants in the A-LONG study developed inhibitors to Eloctate. One participant had a transient, positive neutralising antibody test result, which was not confirmed upon repeat testing. There were no reports of serious vascular (blood) clots or serious allergic reactions. Across the routine prophylaxis and on-demand therapy arms, adverse reactions were reported in 5.5 per cent of participants. These adverse reactions included arthralgia (joint pain), malaise (general discomfort), upper abdominal pain, lower abdominal pain, angiopathy (vascular pain after injection of therapy), bradycardia (slow heart rate), chest pain, cough, dizziness, dysgeusia (taste alteration), feeling cold, feeling hot, headache, hypertension (high blood pressure), joint swelling, myalgia (muscle pain), procedural hypotension (low blood pressure) and rash. Each event occurred in two or fewer study participants. Two participants were withdrawn from the study due to adverse reactions: one participant due to rash and one due to arthralgia.

The pediatric indication for Eloctate is supported by interim safety and PK results in 38 boys ages two to 11 years old from the Phase 3 Kids A-LONG study. These data showed that Eloctate was generally well-tolerated and no inhibitors were detected. The relative increase in half-life (a measure of the time therapy remains in the body) seen with Eloctate was consistent with findings in adults and adolescents. In comparison with adolescents and adults, children two to five years old have a shorter half-life and higher clearance of haemophilic factors (adjusted for body weight); therefore, a higher dose or more frequent dosing may be needed in this age group. In April 2014, Biogen Idec and Swedish Orphan Biovitrum (Sobi) reported positive top-line results from the completed Kids A-LONG study, which confirmed and expanded upon the interim data.

Biogen Idec plans to make Eloctate commercially available to people with hemophilia A in the United States in July 2014. In the US, Biogen Idec will offer a variety of personalised assistance and resources through My Eloctate Services. As part of the company’s global commitment to the haemophilia community, Biogen Idec will provide equitable access to therapy including humanitarian donations.