Fondaparinux

 
 
Fondaparinux is a synthetic truncated heparin like saccharide that is approved for prevention and treatment of deep vein thrombosis (DVT) and pulmonary embolism. It is typically used during hip and knee surgery and as such is universally applicable.
 
It is a pharmaceutically superior compared with other heparin drugs derived from natural sources. It has several advantages as it reduces the risk of side effects such as heparin induced thrombocytopenia (HIT) and has a much longer half life.
 
There is one major drawback with Fondaparinux preventing it from becoming a blockbuster. The manufacturing process is complex and involves an unusually large number of chemical steps and a low overall yield. This means that even though the original patent (®Arixtra) has expired there are few suppliers1 and the price for the generic version remains high. However there are indications for a growing interest from several pharmaceutical companies in exploiting the vast potential market for this drug2.
 
Structurally it consists of a pentasaccharide containing the monosaccharides D-glucosamine (unit A, C and E), L-iduronic acid (unit B) and D-glucuronic acid (unit D), which have a unique sulphation pattern (scheme 1).
 
 
 
Fondaparinux 
Scheme 1: Chemical structure of the pentasaccharide Fondaparinux
 
 
 
 
The structure was identified as the minimum sequence that can inhibit antithrombin (AT-III) in the anticoagulation cascade.
 
 
REFERENCES
 
1. a) The rights for Arixtra and the manufacturing facilities have been taken over by Aspen Pharma from GSK in 2014. b) Generic Fondaparinux is at the moment only produced by Dr. Reddy’s under a licence agreement with Alchemia (e.g. Patent no. US 2015/0005485 A1, issued Jan. 1, 2015)
 
2. a) Apicore US LCC. Patent no. US 2014/0336369 A1, issued Nov. 13, 2014. b) Reliable Biopharmaceutical Corporation. Patent no. US 2015/0018537 A1, issued Jan. 15, 2015. c) Scinopharm Taiwan, LTD. Patent no. US 2015/0031865 A1, issued Jan. 29, 2015.