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Lapaquistat acetate + statin is a combination therapy investigated for the treatment of hypercholesterolemia. Lapaquistat acetate is a small molecule squalene synthase inhibitor that acts downstream of HMG-CoA reductase (the target of statins) in the cholesterol biosynthesis pathway. By inhibiting squalene synthase, it reduces cholesterol synthesis and lowers low-density lipoprotein cholesterol (LDL-C). Statins inhibit HMG-CoA reductase, reducing mevalonate production and upregulating LDL receptors to increase clearance of serum cholesterol. When used together, lapaquistat acetate and statins provide additive reductions in LDL-C levels compared to either agent alone. However, clinical development was terminated due to potential hepatic safety issues observed with lapaquistat acetate[1][2][3].
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