New Nonstatin Lipid-lowering Drugs

New Nonstatin Lipid-lowering Drugs

Challenges

  • Inadequate response in those at high-risk or those with very high low-density lipoprotein cholesterol (LDL-C) levels. Intolerance to available therapy or at higher doses.
  • Short- and long-term side effects of therapy with the current lipid-lowering therapy (LLT).
  • Interaction of LLT with concomitant medication.
  • Inadequate response/benefit from current therapies for raising high-density lipoprotein (HDL).
  • Inadequate response from current therapies for lowering triglyceride (TG).
  • Assessing newer targets to prevent cardiovascular disease (CVD).

Newer drugs in clinical practice

  • PCSK9 inhibitors
    1. Monoclonal antibodies - Evolocumab and alirocumab
    2. PCSK9 inhibitors - siRNA molecule - Inclisiran
  • Bempedoic acid
  • Eicosapentaenoic acid (EPA)

Angiopoietin-like protein 3 (ANGPTL3) is a key modulator of plasma lipoprotein levels. Evinacumab is a full human monoclonal antibody and inhibits ANGPTL3.

Three new drugs targeting Lp(a) are in development; all siRNA-based therapies: Pelacarsen, Olpasiran and SLN360.

Obicetrapib is a selective cholesteryl ester transfer protein (CETP) inhibitor; a daily dose of 10 mg obicetrapib in combination with moderate-intensity statins for 12 weeks resulted in an incremental LDL-C reduction of up to 50% compared with statin monotherapy.

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