Strategies towards a longer acting factor VIII.

ABSTRACT

The reduced mortality, improved joint outcomes and enhanced quality of life, which have been witnessed in the developed world for patients with haemophilia, have been an outstanding achievement. Advancements in biotechnology contributed significantly through the development of improved pathogen screening, viral inactivation techniques and the development of recombinant clotting factors. These were partnered with enhanced delivery of care through comprehensive haemophilia centres, adoption of home therapy and most recently effective prophylaxis. This came at great costs to governments, medical insurers and patients' families. In addition, barriers persist limiting the adoption and adherence of effective prophylactic therapy. Biotechnology has been successful at overcoming similar barriers in other disease states. Long-acting biological therapeutics are an incremental advance towards overcoming some of these barriers. Strategies that have been successful for other therapeutic proteins are now being applied to factor VIII (FVIII) and include modifications such as the addition of polyethylene glycol (PEG) polymers and polysialic acids and alternative formulation with PEG-modified liposomes. In addition, insight into FVIII structure and function has allowed targeted modifications of the protein to increase the duration of its cofactor activity and reduce its clearance in vivo. The potential advantages and disadvantages of these approaches will be discussed.