Abstract
Haemophilia is a rare disease for which the approved therapeutic options have remained virtually unchanged for 50 years. In the past decade, however, there has been an explosion of innovation in the treatment options that are either in development or have been approved for haemophilia, including engineered clotting factors and an extensive pipeline of new approaches and modalities. Several of these new modalities, especially gene therapy, demonstrate proof of principle in haemophilia but could have broader applications. These advances, in combination with better diagnostics, are now enabling clinicians to improve the standard of care for people with haemophilia. The different mechanisms of action and modifications used in these therapies have implications for their safe and efficacious use, which must be balanced with their therapeutic utility. This Review focuses on the biological aspects of the most advanced and innovative approaches for haemophilia treatment and considers their future use.
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T.H. and R.P. are employees of Bioverativ, a Sanofi company.
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Glossary
- Haemostasis
-
Literally means halting of the blood. In this context, haemostasis is the means by which the body maintains the balance between normal blood flow and the clotting process to stop bleeding events.
- Thrombosis
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The pathological formation of a blood clot in a blood vessel.
- Haemophilic arthropathy
-
Permanent joint disease occurring in patients with haemophilia owing to long-term bleeding into the joint (haemarthrosis) and resulting inflammation.
- Cryoprecipitates
-
Insoluble precipitates prepared by slowly thawing fresh-frozen plasma; cryoprecipitates are used as a source of factor VIII but also contain considerable amounts of fibrinogen, von Willebrand factor, FXIII and fibronectin.
- B domain
-
A large protein-coding domain in the middle of the F8 gene that is largely dispensable for the full activity of the protein.
- PEGylated
-
PEGylation is the chemical or enzymatic addition of polyethylene glycol (PEG) molecules to proteins. PEG molecules are synthetic, highly water-soluble polymers with a large hydrodynamic radius and are not degraded by endogenous enzymes. PEG molecules used for half-life extension typically range from 5 to 40 kDa in size.
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Peters, R., Harris, T. Advances and innovations in haemophilia treatment. Nat Rev Drug Discov 17, 493–508 (2018). https://doi.org/10.1038/nrd.2018.70
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DOI: https://doi.org/10.1038/nrd.2018.70
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