Inherited coagulation disorders constitute a broad spectrum of
coagulation factor deficiencies that include X-linked factor (F)VIII or FIX deficiency that causes
haemophilia, and autosomal recessive disorders producing heterogeneous deficiencies in
fibrinogen (FI),
prothrombin (FII), FV, FVII, FX, FXI, FXIII and combined FV+FVIII. Significant advances in treatments for patients with congenital
haemophilia A (FVIII deficiency) and B (FIX deficiency) over the last two decades have resulted from improvements in the production, availability and patient access to factor replacement products. Translation of advances in biotechnology, namely
recombinant protein technology, targeted
protein modifications to improve function and potentially reduce immunogenicity, and advanced formulations to optimize bioavailability and sustain activity offer promisingly new treatments for
haemophilia as well as recessively inherited
bleeding disorders in patients who otherwise have few therapeutic options. Though a theoretical risk remains for blood-borne
viral infections with pooled plasma-derived products, this concern has diminished with breakthroughs in purification and viral inactivation methods. Development of inhibitory
antibodies is still the most daunting problem for patients with inherited
bleeding disorders, complicating treatment approaches to control and prevent
bleeding, and posing risks for allergic and
anaphylactic reactions in susceptible patients. The objectives of this review are to (i) highlight emerging advances in
hemostatic therapies that are bioengineered to improve pharmacokinetic properties and bioavailability, sustain functional activity, and possibly eliminate immunogenicity of recombinant factor
proteins; and (ii) present an overview of key clinical trials of novel factor products currently in the development pipeline.