Unfractionated Heparin (UFH)
Heparin is a sulfated glycosaminoglycan that has been used as an anticoagulant for a wide range of indications since the mid-1930s.
The first and oldest commercially available heparin, called unfractionated heparin (UFH), is extracted from pig intestinal lining. UFH is a heterogeneous, poorly characterized mixture of polysaccharides ranging from 20 to 100 monosaccharide units. Consequently, heparin's potency and potential for side effects can vary from batch-to-batch and from manufacturer to manufacturer.
Low Molecular Weight Heparin (LMWH)
Improved versions of UFH have been developed by controlled enzymatic or chemical de-polymerization, which yield polysaccharides that are shorter than 30 units and are called low molecular weight heparin (LMWH). The major advantage over most unfractionated heparin is to have a better PK/PD profile and to produce fewer side effects. However, manufacturers are still challenged to make homogeneous, reproducible lots and batches. In 2009, Lovenox® (enoxaparin), the leading LMWH, had sales of >$3.0B.
The first synthetic small-glyco drug (Arixtra®)
The first synthetic pentasaccharide to be used as an antithrombotic drug was discovered by the group of Jean Choay, of which Maurice Petitou was a prominent member. In the late 1970s and early 1980s, working on fractions of heparin obtained via degradation and isolation procedures, they identified a pentasaccharide that was the minimal sequence of heparin required to activate antithrombin and induce selective inhibition of factor Xa. This pentasaccharide -fondaparinux- was co-developed by Sanofi and Organon as Arixtra®, the first synthetic and selective factor Xa inhibitor.
The superior risk/benefit ratio of Arixtra® compared to UFH or Lovenox® has been demonstrated in the prevention of venous thromboebolism and the treatment of acute coronary syndromes (ACS).
The next generations (Endotis)
Using our oligosaccharide expertise combined with medicinal chemistry, we have now developed the next generation of anticoagulant: a potent synthetic neutralizable anticoagulant for use in extra corporeal circulation (ECC) during cardiac surgery and other high value medical indications.
We are also developing orally availably compounds, neutralizable or not for the prevention and treatment of venous and arterial thrombosis.
