Developing the First Recombinant Factor XIII for Congenital Factor XIII Deficiency: Clinical Challenges and Successes

• Published in: Seminars in thrombosis and hemostasis Vol. 43; no. 1; p. 59
• Main Authors: Carcao, Manuel, Fukutake, Katsuyuki, Inbal, Aida, Kerlin, Bryce, Lassila, Riitta, Oldenburg, Johannes, Garly, May-Lill, Nugent, Diane
• Format: Journal Article
• Language: English
• Published: United States 01.02.2017
• Subjects: Factor XIII - therapeutic use; Factor XIII Deficiency - drug therapy; Humans; Recombinant Proteins - therapeutic use
• ISSN: 1098-9064
• DOI: 10.1055/s-0036-1585076

Congenital factor XIII (FXIII) deficiency is a rare, autosomal recessive bleeding disorder with potentially life-threatening consequences. FXIII is composed of two subunits (A and B), and a deficiency or dysfunction of either can result in FXIII deficiency. Traditionally, FXIII deficiency has been managed by infusing plasma-derived products containing FXIII (fresh frozen plasma, cryoprecipitate, and plasma-derived FXIII concentrates), all of which contain both subunits. Despite the increased safety of plasma-derived products, concern remains regarding potential viral safety issues. This review describes the development, from concept to clinical use, of a recombinant FXIII molecule (containing subunit A only; rFXIII-A ) for congenital FXIII-A subunit deficiency. Unmet needs and ongoing challenges in congenital FXIII deficiency are also discussed. Despite the challenges in developing a product for a very rare bleeding disorder, the information gathered on efficacy, safety, and pharmacokinetics of FXIII replacement therapy represents the largest dataset on congenital FXIII-A subunit deficiency in the world. It also provides evidence for the safety and efficacy of monthly prophylaxis with 35 IU/kg of rFXIII-A in patients with FXIII-A subunit deficiency. The issues encountered and overcome, along with lessons learned, may be applied to and encourage the development of new recombinant products for other rare bleeding disorders.