Global biotherapeutics leader CSL Behring announced that the company has submitted its Marketing Authorisation Application (MAA) to the European Medicines Agency (EMA) for its novel investigational recombinant factor VIII single-chain (rVIII-SingleChain) for the treatment of haemophilia A. In the pivotal clinical trial, rVIII-SingleChain met all primary endpoints.

Haemophilia A is a congenital bleeding disorder characterized by deficient or defective factor VIII; nearly all affected patients are male. People with haemophilia A may experience prolonged or spontaneous bleeding, especially into the muscles, joints, or internal organs. According to the World Federation of Haemophilia, about 1 in 10,000 people are born with haemophilia, the majority of whom have haemophilia A.

“Our focused research and development and strong relationship with the bleeding disorders community led us to seek further advancements in the care and treatment of haemophilia,” said Dr. Andrew Cuthbertson, chief scientific officer and director of R&D, CSL Limited. “Today, we have the only recombinant single-chain factor VIII product in late-stage development for the management of haemophilia A. We look forward to, upon approval, providing this innovative specialty biotherapy to patients in the EU and European Economic Area.”

The MAA is based on the AFFINITY clinical development programme, which includes a phase I/III open-label, multi-center trial examining safety and efficacy. The pharmacokinetics of rVIII-SingleChain compared with recombinant human antihemophilic factor VIII (octocog alfa) was also studied.

Results from the phase I/III study presented earlier this year at the International Society on Thrombosis and Haemostasis (ISTH) congress in Toronto showed that patients treating prophylactically had a median annualized bleeding rate (ABR) of 1.14 and a median annualized spontaneous bleeding rate (AsBR) of 0.00. The data also showed that, of 848 bleeds treated in the study, 94 per cent were controlled with no more than two infusions of rVIII-SingleChain, with 81 per cent controlled by one infusion. Moreover, hemostatic control of a bleeding event treated with rVIII-SingleChain was assessed by the investigator as excellent or good 94 per cent of the time (835 assessed bleeding events).

The results presented at ISTH included data on more than 14,000 exposure days in 146 patients on prophylaxis and 27 patients treating on demand for a bleeding event. In total, 120 patients were treated for more than 50 days of exposure; 52 had more than 100 days of exposure. In the prophylaxis group, 32 per cent of patients were dosed twice weekly and 54 per cent received treatment three times per week; the regimen was determined by the investigator. The most common adverse events were naso-pharyngitis, arthralgia, and headache. No inhibitors were reported.

Specifically designed for greater molecular stability, rVIII-SingleChain is the first and only recombinant single-chain factor VIII (FVIII) product in late-stage development for the treatment of hemophilia A. rVIII-SingleChain has a strong affinity for von Willebrand factor, leading to greater stability and integrity of factor VIII in circulation. The stability of rVIII-SingleChain leads to a longer-lasting therapeutic effect with reduced dosing frequency. In July 2015, the US Food and Drug Administration accepted for review CSL Behring’s Biologics License Application for rVIII-SingleChain.