Are Monoclonal Antibodies Effective in Treating High Cholesterol?

Monoclonal antibodies are the antibodies produced in the laboratory which can increase, copy, or restore the immune system’s response to certain antigens. One such monoclonal antibody, Evinacumab was able to reduce the levels of Low Density Lipoprotein (LDL) which is often termed as the bad cholesterol by 50%. The decrease in level of LDL was observed in patients who had very high levels of cholesterol which did not respond to the standard treatment. The study was conducted by Icahn School of Medicine of Mount Sinai and was published in The New England Journal of Medicine.

In Familial hypercholesterolemia, which is a common inherited condition difficult to treat, evinacumab combined with maximally-tolerated doses of other cholesterol-lowering drugs showed good result in reducing the high cholesterol levels. The mechanism of action of evinacumab is different than the existing drugs.

The principal investigator of the study Robert Rosenson, Professor of Medicine and Director of Cardiometabolic disorders at the Icahn School of medicine at Mount Sinai said,“Our study assessing the safety and efficacy of evinacumab shows that it can lower LDL cholesterol by half in patients unable to attain target guidelines despite maximally tolerated lipid lowering therapy. Evinacumab is a fully human monoclonal antibody that inhibits angiopoietin like protein 3 (ANGPLT3) and lowers LDL cholesterol through an LDL receptor independent pathway. Genetic studies have shown that people who are missing or have low levels of ANGPTL3 are known to have very low lifelong levels of LDL cholesterol and rarely suffer from atherosclerotic cardiovascular disease.”

Severe hypercholesterolemia (increased cholesterol) is having untreated LDL cholesterol value greater than or equal to 190mg/dl. Familial hypercholesterolemia is commonly seen in patients with early-onset cardiovascular disease. According to the American Heart Association/American Congress of Cardiology guidelines, the recommended levels of LDL in patients with high risk of cardiovascular disease is less than or equal to 70mg/dl.

The standard triple therapy of a high intensity statin (slows cholesterol production), PCSK9 inhibitor (binds to PCSK9 protein), ezetimibe (decreases cholesterol absorption from the intestine) does not show much benefit in patients with hypercholesterolemia.

Dr Rosenson says,“There's an unmet need for agents that address refractory hypercholesterolemia through a pathway that's independent of the LDL receptor. If approved by the U.S. Food and Drug Administration, evinacumab may potentially fill that clinical gap for patients, by reducing severely elevated LDL cholesterol."

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In the clinical trials conducted, it was observed that evinacumab was well tolerated by patients. Certain side effects seen included difficulty breathing observed in one patient on subcutaneous administration and another patient had a mild anaphylactic reaction (rash, vomiting, nausea, difficulty breathing). For these patients, the medication was immediately stopped and other treatments were given. Due to certain comorbidities, two deaths occurred during the trial.

Heterozygous familial hypercholesterolemia (HeFH) is a type of familial hypercholesterolemia caused by a mutation in the LDL receptor gene. Dr Rosenson said,“Our study demonstrates that a regimen of either subcutaneous or intravenous evinacumab can have a significant impact on LDL cholesterol. If approved for use in this setting, evinacumab could potentially arm cardiologists with a major new add-on therapy to bring patients with HeFH to or closer to their cholesterol-lowering goal.”

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In the United States and the European Union, evinacumab is under regulatory review as an addition to other cholesterol-lowering agents in patients with different types of familial hypercholesterolemia.

Source-Medindia