Varespladib
Encyclopedia
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
. Since 2006, it has been under active investigation by Anthera Pharmaceuticals
as a potential therapy for several inflammatory diseases, including acute coronary syndrome
and acute chest syndrome
.
Varespladib is being studied in both oral and intravenous dosage forms.
(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.
Enzyme inhibitor
An enzyme inhibitor is a molecule that binds to enzymes and decreases their activity. Since blocking an enzyme's activity can kill a pathogen or correct a metabolic imbalance, many drugs are enzyme inhibitors. They are also used as herbicides and pesticides...
of the IIa, V, and X isoforms of secretory phospholipase A2 (sPLA2). The molecule
Molecule
A molecule is an electrically neutral group of at least two atoms held together by covalent chemical bonds. Molecules are distinguished from ions by their electrical charge...
acts as an anti-inflammatory agent by disrupting the first step of the arachidonic acid pathway of inflammation
Inflammation
Inflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...
. Since 2006, it has been under active investigation by Anthera Pharmaceuticals
Anthera Pharmaceuticals
Anthera Pharmaceuticals, Inc. is a pharmaceutical company that specializes in developing treatments for serious cardiovascular and autoimmune diseases...
as a potential therapy for several inflammatory diseases, including acute coronary syndrome
Acute coronary syndrome
Acute coronary syndrome is usually one of three diseases involving the coronary arteries: ST elevation myocardial infarction , non ST elevation myocardial infarction , or unstable angina ....
and acute chest syndrome
Acute chest syndrome
The acute chest syndrome is a noninfectious vaso-occlusive crisis of the pulmonary vasculature commonly seen in patients with sickle cell anemia.It is characterized by a new infiltrate on a chest x-ray.-Cause:...
.
Varespladib is being studied in both oral and intravenous dosage forms.
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 is under evaluation by Anthera Pharmaceuticals as an anti-inflammatory sPLA2 inhibitor for the prevention of acute chest syndromeAcute chest syndrome
The acute chest syndrome is a noninfectious vaso-occlusive crisis of the pulmonary vasculature commonly seen in patients with sickle cell anemia.It is characterized by a new infiltrate on a chest x-ray.-Cause:...
(ACS), the leading cause of death for patients with sickle-cell disease
Sickle-cell disease
Sickle-cell disease , or sickle-cell anaemia or drepanocytosis, is an autosomal recessive genetic blood disorder with overdominance, characterized by red blood cells that assume an abnormal, rigid, sickle shape. Sickling decreases the cells' flexibility and results in a risk of various...
.
Elevated serum
Blood serum
In blood, the serum is the component that is neither a blood cell nor a clotting factor; it is the blood plasma with the fibrinogens removed...
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
Vaso-occlusive crisis
A vaso-occlusive crisis is a common painful complication of sickle cell anemia in adolescents and adults. It is a form of sickle cell crisis. It occurs when the circulation of blood vessels is obstructed by sickled red blood cells, causing ischemic injuries...
, or in patients with respiratory diseases such as pneumonia
Pneumonia
Pneumonia is an inflammatory condition of the lung—especially affecting the microscopic air sacs —associated with fever, chest symptoms, and a lack of air space on a chest X-ray. Pneumonia is typically caused by an infection but there are a number of other causes...
. A reduction in serum sPLA2 levels, for example through blood transfusion
Blood transfusion
Blood transfusion is the process of receiving blood products into one's circulation intravenously. Transfusions are used in a variety of medical conditions to replace lost components of the blood...
, 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
Eli Lilly and Company
Eli Lilly and Company is a global pharmaceutical company. Eli Lilly's global headquarters is located in Indianapolis, Indiana, in the United States...
and Shionogi
Shionogi
is a Japanese pharmaceutical company best known for developing Crestor. Medical supply and brand name also uses Shionogi .Shionogi has business roots that date back to 1878, and was incorporated in 1919. Among the medicines produced are for hyperlipidaemia, antibiotics, and cancer medicines.In...
in 2006. In 2007, the U.S. Food and Drug Administration
Food and Drug Administration
The Food and Drug Administration is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments...
(FDA) granted varespladib sodium orphan drug
Orphan drug
An orphan drug is a pharmaceutical agent that has been developed specifically to treat a rare medical condition, the condition itself being referred to as an orphan disease...
status for its potential to treat patients with sickle-cell disease. In 2009, Anthera Pharmaceuticals completed a Phase II study of varespladib sodium.