Novel Drug Approaches in Development for the Treatment of Lipid Disorders

Abstract

Lipid-lowering drug therapy with statins has become a cornerstone to reduce and prevent atherosclerosis and its detrimental complications like cardiovascular diseases and stroke. Due to the multifactorial pathogenesis of atherosclerosis the search for novel lipid-modifying drugs is still one of the most active areas in research and development in the pharmaceutical industry. Currently, the focus lies on novel LDL-cholesterol lowering drugs with a higher efficacy and improved safety profile as well as on approaches to increase plasma levels and functionality of high-density lipoproteins (HDL) based on the inverse relationship between high plasma HDL-levels and the risk for cardiovascular diseases. Whereas the today clinically used lipid-modifying drugs are predominantly small molecules for oral drug therapy a significant percentage of the drug candidates currently in development are biological drugs such as monoclonal antibodies and antisense oligonucleotides. Up-to-date around 70 novel drug molecules acting on about 20 different molecular targets are in clinical and preclinical development with antibodies inhibiting proprotein convertase subtilisin/kexin type 9 (PCSK9) being the most intensively investigated and competitive approach. The clinical results reported so far with these antibodies are very promising whereas the clinical benefit for prevention of atherosclerosis and cardiovascular diseases by pharmacologically increasing of plasma high-density lipoproteins still remains to be demonstrated. However, with the recent approval of 2 innovative drugs for the treatment of familial hypercholesterolemia and the promising clinical results of several novel drug candidates for LDL cholesterol lowering and high-density lipoprotein modulation one can expect the appearance of new drug breakthroughs for the treatment of dyslipidemia in the near future.

Key words

dyslipidemia - novel lipid-modifying drugs - drug development pipeline

• References

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