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lapaquistat acetate + lipid-lowering therapy
- Development stage
- Discontinued
- Lead developer
- Takeda
- Modality
- Small Molecules
- Administration
- Oral
01
Overview
Lapaquistat acetate + lipid-lowering therapy is a combination approach investigated for the treatment of hypercholesterolemia, comprising lapaquistat acetate—a small molecule squalene synthase inhibitor—with standard lipid-lowering agents, mainly statins or other antihyperlipidemic drugs. Lapaquistat acetate inhibits squalene synthase, an enzyme downstream of HMG-CoA reductase in the cholesterol biosynthesis pathway, thereby reducing cholesterol synthesis at a different step than statins. Clinical trials evaluating this combination investigated efficacy and safety in lowering low-density lipoprotein cholesterol (LDL-C) and other lipid fractions, showing additional LDL-C reduction when lapaquistat was co-administered with statins compared to statin monotherapy. However, development was discontinued due to hepatotoxicity risks at higher doses and lack of sufficient additional efficacy at safe lower doses, as well as unfavorable risk–benefit and commercial viability compared to existing therapies[1][2][5][6].
- Other names
- lapaquistat acetate + lipid-lowering therapy
02
Targets
FDFT1 (Squalene synthase)
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