Biogen Idec and Swedish Orphan Biovitrum (Sobi),  an international healthcare company dedicated to bringing innovative therapies and services to improve the lives of rare disease patients,  have released data that confirmed the ability of investigational recombinant factors VIII Fc fusion protein (rFVIIIFc) and IX Fc fusion protein (rFIXFc) to provide long-lasting protection from bleeding with fewer injections than are required with the current standard of care for people with haemophilia.

The data, from the largest phase III registrational studies conducted in haemophilia to date, were presented at the 6th Annual Congress of the European Association for Haemophilia and Allied Disorders (EAHAD).

The studies compared the pharmacokinetic activity of rFVIIIFc for haemophilia A and rFIXFc for haemophilia B to currently available treatments. In the studies, the long-lasting candidates stayed active in the body longer, enabling study participants to prevent bleeding with less frequent injections than are required with the current standard of care. In the A-LONG study, patients with haemophilia A were able to use once to twice weekly prophylactic (preventative dosing) injections of rFVIIIFc while maintaining low bleeding rates. In the B-LONG study, rFIXFc allowed patients with haemophilia B to use prophylactic injections every one to two weeks with low bleeding rates.

“Data from these phase III trials demonstrate a potential to transform the treatment of haemophilia by offering long-lasting protection from bleeding while meaningfully reducing treatment burden associated with this rare disease,” said Glenn Pierce, MD, PhD., senior vice president of Global Medical Affairs and chief medical officer of Biogen Idec’s haemophilia therapeutic area. “Less frequent injections may help more people with hemophilia adhere to a preventative treatment schedule, which can help prevent the long-term health consequences associated with treating a bleed after it occurs.”

According to the National Haemophilia Foundation's Medical and Scientific Advisory Council guidelines, the current standard of care for haemophilia A and B requires frequent injections, which are a burden for patients. Prophylactic treatment for haemophilia A typically requires injections three times per week or every other day, and injections two to three times per week for the treatment of haemophilia B. People with severe haemophilia who do not follow a prophylactic injection schedule remain vulnerable to bleeding that can cause irreversible joint damage and life-threatening haemorrhages.

Recombinant FVIIIFc and recombinant FIXFc were developed using Fc fusion technology, which has safely been used in FDA-approved medicines for more than a decade. Biogen Idec and Sobi applied Fc fusion technology in haemophilia for the first time with the goal of making clotting factors last longer and reduce the burden of injections for patients and their families.

The A-LONG results confirm the long-lasting characteristics of rFVIIIFc; specifically, the data show that rFVIIIFc stays in the body for 50 per cent longer than Advate [anti-hemophilic factor (recombinant), plasma/albumin-free method], the most frequently used factor VIII therapy. In the trial, the terminal half-life for rFVIIIFc was 19 hours compared to 12 hours for Advate. Other measures of rFVIIIFc’s activity in the body reinforce its long-lasting characteristics: the mean time for maintaining a clotting factor activity level associated with less bleeding (time to one per cent) was approximately five days for rFVIIIFc compared to 3.5 days for Advate and the average rate at which rFVIIIFc was cleared from the body was 2.0 mL/hr/kg compared with 3.0 mL/hr/kg for Advate. In the study’s individualized prophylaxis arm, patients received rFVIIIFc at a median dosing interval of 3.5 days and a median weekly dose of 78 IU per kg to prevent bleeding, which compares favorably to the recommended dose for the standard of care. Nearly one-third of patients were able to achieve every five day dosing in this arm. Overall, the A-LONG data indicate that rFVIIIFc has the potential to become the first product to offer hemophilia A patients long-lasting protection from bleeding with less frequent dosing than the current standard of care.

The B-LONG results confirm the long-lasting characteristics of rFIXFc; specifically, the data show that rFIXFc stays in the body for more than twice as long as BeneFIX [Coagulation Factor IX (Recombinant)], the only recombinant factor IX therapy currently approved for prophylactic use. The terminal half-life for rFIXFc was 82 hours compared to 34 hours for BeneFIX. Other measures of rFIXFc’s activity in the body reinforce its long-lasting characteristics: the mean time for maintaining a normal clotting factor activity level (time to one per cent) was 11 days for rFIXFc compared to five days for BeneFIX and the average rate at which rFIXFc was cleared from the body was 3.2 mL/hr/kg compared with 6.3 mL/hr/kg for BeneFIX. All patients in the individualized interval prophylaxis arm of the study were able to go at least one week between rFIXFc injections and 50 percent were able to go 14 days or longer before needing another dose to prevent bleeding. The median weekly dose was 45 IU per kg, comparable to the recommended dose for the current standard of care. Overall, the B-LONG data support the potential for rFIXFc to become the first product to offer hemophilia B patients long-lasting protection from bleeding with a more convenient injection schedule than the current standard of care.

Importantly, the difference in the duration of activity of rFVIIIFc and rFIXFc was expected and consistent with the differences between the natural clotting factors that these products augment. Fc Fusion technology extends FVIII and FIX differently based on the biological differences in haemophilia A and B. The length of time that FVIII stays active is dictated by its own duration as well as that of the blood protein that it binds to, known as von Willebrand factor. The activity of FIX is not restricted in this way.

“These new data support the application of Fc fusion technology in haemophilia, using a naturally occurring pathway to delay the breakdown of factor in the body and cycle it back into the bloodstream,” said Birgitte Volck, MD, Ph.D., senior vice president & chief medical officer of Sobi. “While Fc fusion has been used in medicines for more than a decade, rFVIIIFc and rFIXFc are the first investigational therapies to use the technology to successfully extend the half-lives of clotting factors, which could offer protection from bleeding while reducing the burden of injections for people with haemophilia.”

Recombinant FVIIIFc and recombinant FIXFc are clotting factors developed using Biogen Idec’s novel and proprietary monomeric Fc fusion technology, which makes use of a naturally occurring pathway that delays the breakdown of factor in the body and cycles it back into the bloodstream, enabling it to remain in the body longer following an injection. Fc fusion technology is used in seven FDA-approved products for the long-term treatment of chronic diseases including rheumatoid arthritis, psoriasis and platelet disorders.

Biogen Idec and Sobi are partners in the development and commercialization of rFVIIIFc and rFIXFc. Biogen Idec leads development, has manufacturing rights, and has commercialization rights in North America and all other regions excluding the Sobi territory. Sobi has the right to opt in to assume final development and commercialization in Europe, Russia, the Middle East and Northern Africa.

Biogen Idec discovers, develops and delivers to patients worldwide innovative therapies for the treatment of neurodegenerative diseases, haemophilia and autoimmune disorders.