varespladib-methyl and Acute-Coronary-Syndrome

Anthera Pharmaceuticals is developing an oral formulation of varespladib (A 001; A 002; A-001; A-002; LY 315920; LY 333013; LY315920; LY333013; S 3013; S 5920; S-3013; S-5920; Varespladib methyl) for once-daily treatment of acute coronary syndromes. Varespladib acts by inhibiting secretory phospholipase A2 (sPLA2) and the drug is currently being evaluated in approximately 6500 patients with acute coronary syndromes receiving atorvastatin in the placebo-controlled VISTA 16 (NCT01130246) trial being conducted in North America and Europe. This review discusses the development history and scientific profile of this new compound.

Topics: Acetates; Acute Coronary Syndrome; Animals; Clinical Trials as Topic; Humans; Indoles; Keto Acids

The action of secretory phospholipase A(2) (sPLA(2)) on lipoproteins may render them more susceptible to oxidation, thereby promoting vascular inflammation and increasing cardiovascular risk. Patients with acute coronary syndrome face a high risk of early, recurrent cardiovascular events that is associated with biomarkers of inflammation, including sPLA(2). The Vascular Inflammation Suppression to Treat Acute Coronary Syndrome for 16 Weeks (VISTA-16, NCT01130246) tests the hypothesis that varespladib methyl, an inhibitor of several sPLA(2) isoforms with a causal role in atherosclerosis, reduces cardiovascular risk among patients with acute coronary syndromes.. Up to 6,500 patients with acute coronary syndrome will be randomized to receive treatment with varespladib methyl 500 mg daily or placebo for 16 weeks, in addition to background treatment with atorvastatin and other evidence-based therapies. The primary efficacy parameter is the combination of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke or hospitalization for unstable angina with objective evidence of myocardial ischemia. Effects of varespladib methyl on lipid and inflammatory markers, in addition to safety and tolerability, will also be evaluated.. sPLA(2) inhibition has the potential to exert a favorable effect on the artery wall. The VISTA-16 study will determine whether varespladib methyl has a beneficial impact on cardiovascular events in patients with an acute coronary syndrome.

Topics: Acetates; Acute Coronary Syndrome; Atorvastatin; Double-Blind Method; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Indoles; Inflammation; Keto Acids; Phospholipases A2, Secretory; Pyrroles

Secretory phospholipase A(2) group IIA (sPLA(2-)IIA) concentration and activity are associated with increased risk of cardiovascular events in acute coronary syndrome (ACS) patients. This study evaluated baseline differences in sPLA(2)-IIA concentration and other inflammatory markers in ACS patients with and without diabetes, and the inflammatory biomarker response to selective sPLA(2) inhibition.. The effects of the sPLA(2) inhibitor varespladib methyl 500 mg daily and placebo on serial changes in inflammatory and lipid biomarkers were examined in 624 ACS patients who were treated with standard of care including atorvastatin 80 mg daily.. Compared with non-diabetic patients, diabetic patients had higher baseline concentrations of sPLA(2)-IIA (p = 0.0066), hs-CRP (p = 0.0155), and IL-6 (p = 0.009). At 8 weeks of treatment (primary endpoint), varespladib methyl reduced median sPLA(2)-IIA levels by -83.6% in diabetic patients and by -82.4% in non-diabetic patients (p = 0.33). Median hs-CRP and IL-6 levels were reduced in both varespladib methyl-treated diabetic and non-diabetic patients, but these differences were not statistically significantly different at 8 weeks (p = 0.57 and p = 0.97 respectively).. Varespladib significantly reduces the post-ACS inflammatory response in those with and without diabetes. These responses were greater in diabetic subjects compared to non-diabetic subjects.

Topics: Acetates; Acute Coronary Syndrome; Anti-Inflammatory Agents; Atorvastatin; Biomarkers; C-Reactive Protein; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Female; Group II Phospholipases A2; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Indoles; Interleukin-6; Keto Acids; Male; Middle Aged; Pyrroles; Treatment Outcome