Biogen Idec and Swedish Orphan Biovitrum (SOBI) announced phase I/II a trial data showing that the companies' long-lasting fully-recombinant factor VIII Fc fusion protein (rFVIIIFc) was well tolerated and demonstrated an approximately 1.7-fold increase in half-life compared with Advate (antihemophilic factor recombinant, plasma/albumin-free method, rFVIII), a commercially-available factor VIII product, in 16 previously-treated patients with severe haemophilia A. The findings, which were seen consistently across all patients and dose levels, are being presented at the XXIIIrd Congress of the International Society on Thrombosis and Haemostasis (ISTH) in Kyoto, Japan.

“This trial is a step toward addressing the significant unmet need for a long-lasting recombinant factor VIII product,” said Neil Josephson, MD, co-principal Investigator of the phase III rFVIIIFc A-LONG trial and associate professor of Medicine in the Division of Haematology at the University of Washington School of Medicine, Seattle, Wash. “Results from the phase I/II a study show that rFVIIIFc has an extended half-life, which may have the potential to provide extended protection from bleeding and reduce the number of infusions necessary for prophylactic treatment of severe haemophilia A.”

Currently, prophylactic treatment of severe haemophilia A requires intravenous infusions three times a week or every other day. rFVIIIFc is a fully-recombinant and fully-active clotting factor designed to replace the protein that haemophilia A patients lack and to last longer in the body than commercially-available factor VIII products. Developed using Biogen Idec's proprietary Fc fusion technology, rFVIIIFc utilizes a natural pathway that recycles rFVIIIFc in the circulation to extend its half-life.

“Biogen Idec is driven to deliver innovative treatments that can make much-needed progress for people with haemophilia,” said Glenn Pierce, MD, PhD, senior vice president of Haemophilia at Biogen Idec. “These study results demonstrate the potential of our Fc fusion technology to develop long-lasting clotting factors that may significantly reduce the burden of treatment and improve quality of life for people with haemophilia.”

“These results are promising and supported the advancement of rFVIIIFc into a phase III trial last year,” said Peter Edman, PhD, chief scientific officer of Swedish Orphan Biovitrum. “We are excited about the potential of rFVIIIFc to make a positive impact on the health and quality of life of haemophilia A patients by providing extended protection from bleeding.”

rFVIIIFc is currently being studied in a registrational, open-label, multi-centre trial (A-LONG), which is evaluating its safety, pharmacokinetics and efficacy in the prevention and treatment of bleeding in previously-treated patients with severe haemophilia A.

Additionally, the European Medicines Agency's (EMA) Paediatric Committee recently adopted an opinion agreeing to the paediatric investigational plan for rFVIIIFc. In accordance with the opinion, Biogen Idec and Swedish Orphan Biovitrum plan to initiate a global paediatric trial in previously-treated patients under 12 years of age as soon as sufficient data are available from a study of older patients. Under draft guidelines published by the EMA for the development of factor VIII products, paediatric data from this trial will be required in the initial submission of a Marketing Authorization Application to the European regulatory agency.

The phase I/II a open-label, cross-over, multi-centre, dose-escalation study evaluated the safety and pharmacokinetics of an intravenous injection of rFVIIIFc in 16 previously-treated patients with severe haemophilia A. The primary objective of the study was to assess the safety of rFVIIIFc at different doses; the secondary objective was to estimate the pharmacokinetic parameters of rFVIIIFc at doses ranging from 25 to 65 IU/kg.

rFVIIIFc was well tolerated in this single-dose study, with no drug-related serious adverse events. Adverse events were observed in 11 out of 16 patients, with one related to study drug - dysguesia (abnormal taste in the mouth). There were no signs of injection site reactions, inhibitor development or anti-rFVIIIFc drug antibodies.

rFVIIIFc demonstrated an approximately 1.7-fold increase in half-life compared to Advate. Other PK parameters such as mean residence time and Area Under the Curve (AUC) were similarly increased. Furthermore, peak plasma concentration and AUC also demonstrated an increase proportional to the dose administered relative to Advate. Advate and rFVIIIFc had comparable and dose-dependent peak plasma concentration, and comparable recovery.

Fc Fusion Technology and the Long-Lasting Recombinant Hemophilia Programme developed using Biogen Idec's proprietary Fc fusion technology, rFVIIIFc utilizes a natural pathway that recycles rFVIIIFc in the circulation to extend its half-life and allow factor to remain in the body longer after an infusion.

Using the same, natural Fc fusion technology as rFVIIIFc, Biogen Idec and Swedish Orphan Biovitrum are also developing a fully-recombinant, long-lasting Factor IX Fc fusion protein (rFIXFc) for the treatment of haemophilia B. rFIXFc is currently being tested in a registrational, open-label, multi-centre trial (B-LONG), which is designed to evaluate its safety, pharmacokinetics and efficacy in prevention and treatment of bleeding in haemophilia B patients.

Haemophilia A is a rare, inherited disorder in which the ability of a person's blood to clot is impaired. It occurs in about one in 5,000 male births annually and is caused by having substantially reduced or no factor VIII protein, which is needed for normal blood clotting. People with haemophilia A therefore need injections of factor VIII to restore the coagulation process and prevent frequent bleeds that could otherwise lead to pain, irreversible joint damage and life-threatening haemorrhages. Prophylactic treatment with infusions three times per week or every other day to maintain a sufficient circulating level of coagulation factor is being increasingly used, and long-term studies demonstrate that such regimens increase the patient's life expectancy and greatly reduce, if not eliminate, progressive joint deterioration.

Biogen Idec uses cutting-edge science to discover, develop, manufacture and market therapies for serious diseases with a focus on neurology, immunology and haemophilia.

Swedish Orphan Biovitrum (Sobi) is a leading European specialty pharmaceutical company focused on providing and developing specialty pharmaceuticals for patients with rare diseases and significant medical needs.