Pregnancy
category — Legal status investigational PubChem CID 155815 | ATC code none CAS Number 172732-68-2 ChemSpider 137248 | |
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Varespladib is an inhibitor of the IIa, V, and X isoforms of secretory phospholipase A2 (sPLA2). The molecule acts as an anti-inflammatory agent by disrupting the first step of the arachidonic acid pathway of inflammation. From 2006 to 2012, varespladib was under active investigation by Anthera Pharmaceuticals as a potential therapy for several inflammatory diseases, including acute coronary syndrome and acute chest syndrome. The trial was halted in March 2012 due to inadequate efficacy.
Intravenous varespladib
Varespladib sodium (also known as A-001, previously LY315920 and S-5920) is a sodium salt of varespladib designed for intravenous delivery. It was under evaluation by Anthera Pharmaceuticals as an anti-inflammatory sPLA2 inhibitor for the prevention of acute chest syndrome (ACS), the leading cause of death for patients with sickle-cell disease.
Elevated serum levels of sPLA2 have been observed in sickle-cell patients preceding and during ACS episodes. This profound elevation in sPLA2 levels is not observed in sickle-cell patients at steady-state or during a vaso-occlusive crisis, or in patients with respiratory diseases such as pneumonia. A reduction in serum sPLA2 levels, for example through blood transfusion, reduces the risk of an ACS, suggesting that sPLA2 plays an important role in the onset of ACS.
Anthera Pharmaceuticals acquired varespladib sodium from Lilly and Shionogi in 2006. In 2007, the U.S. Food and Drug Administration (FDA) granted varespladib sodium orphan drug status for its potential to treat patients with sickle-cell disease. In 2009, Anthera Pharmaceuticals completed a Phase II study of varespladib sodium in subjects with sickle cell disease at risk for ACS.