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Evinacumab-dgnb (Evkeeza-REGN1500), A Novel Lipid-Lowering Therapy for Homozygous Familial Hypercholesterolemia
Raechel T White1, Kjersten H Sankey2, James J Nawarskas1
1From the Department of Pharmacy Practice and Administrative sciences, College of Pharmacy, University of New Mexico Health Science Center, Albuquerque, NM.
Insights
Evinacumab effectively lowers low-density lipoprotein (LDL) by inhibiting ANGPTL3, offering a new option for familial hypercholesterolemia. Further research is needed to confirm its cardiovascular event reduction benefits.
Area of Science:
- Cardiovascular Medicine
- Pharmacology
- Lipid Metabolism
Background:
- Chronically elevated low-density lipoprotein (LDL) contributes to atherosclerosis, increasing risks of coronary heart disease and stroke.
- Familial hypercholesterolemia presents challenges in achieving adequate LDL reduction, despite existing therapies like statins and PCSK9 inhibitors.
- Current LDL-lowering treatments often fail to meet guideline targets for many patients with familial hypercholesterolemia.
Purpose of the Study:
- To evaluate the efficacy and safety of evinacumab, a novel ANGPTL3 inhibitor, in managing lipid levels.
- To explore the potential role of evinacumab in patients with familial hypercholesterolemia who have not achieved LDL goals.
Main Methods:
- Evinacumab inhibits angiopoietin-like protein 3 (ANGPTL3), a protein that regulates lipoprotein metabolism.
- By blocking ANGPTL3, evinacumab promotes the degradation of triglyceride-rich lipoproteins, indirectly reducing LDL cholesterol.
- Clinical trial data were reviewed to assess evinacumab's impact on LDL, HDL, and triglyceride levels.
Main Results:
- Clinical trials indicate that evinacumab is safe and effective in significantly reducing LDL cholesterol levels.
- The therapy has demonstrated a positive effect on overall lipid profiles, including reductions in HDL and triglycerides.
- Adverse effects are generally mild, primarily infusion reactions, nasopharyngitis, and influenza-like symptoms.
Conclusions:
- Evinacumab represents a promising novel therapy for lowering LDL cholesterol, particularly in challenging cases like familial hypercholesterolemia.
- While effective for LDL reduction, its impact on cardiovascular event reduction requires further investigation.
- Its current role may be most defined for patients with homozygous familial hypercholesterolemia, pending long-term outcome data and cost-effectiveness analysis.
Abstract:
Chronically elevated low-density lipoprotein (LDL) has harmful effects on the vasculature including increased vasoconstriction and the formation of plaques which may rupture, causing coronary heart disease and stroke. In patients with familial hypercholesterolemia, adequate reduction of LDL is especially challenging. Although HMG-CoA reductase inhibitors (statins) are the mainstays for LDL lowering, other treatments such as proprotein convertase subtilisin/kexin type 9 inhibitors, bempedoic acid, incliseran, lomitapide, and apheresis have been employed in an effort to achieve adequate LDL reduction in these patients. Despite these available therapies, many patients with familial hypercholesterolemia do not meet the LDL targets suggested in current guidelines. Evinacumab is a novel lipid-lowering therapy that exerts its LDL-lowering effect through inhibition of angiopoietin-like protein 3 (ANGPTL3). ANGPTL3 inhibits the breakdown of triglyceride-rich lipoproteins, such as very low-density lipoprotein and chylomicrons. By inhibiting ANGPTL3, evinacumab allows these lipoproteins to be degraded, ultimately leading to reductions in LDL, high-density lipoprotein, and triglycerides. Clinical trials have demonstrated evinacumab to be safe and effective in reducing LDL. However, data are lacking regarding its potential to reduce risk of atherosclerotic cardiovascular disease. Evinacumab is generally well tolerated with the primary adverse effects comprising infusion reactions, nasopharyngitis, influenza-like illness, dizziness, rhinorrhea, and nausea. While evinacumab is an interesting therapy, until it is proven to reduce cardiovascular events, its high cost leaves its anticipated role in therapy somewhat ambiguous. In the meantime, it may be a useful therapy for those with homozygous familial hypercholesterolemia.
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