Monoclonal antibody drug Evinacumab can reduce LDL cholesterol in high risk patients, reveals study
Mild side effects of evinacumab include difficulty breathing and mild anaphylactic reaction, yet this drug is well-tolerated by most patients without any severe side effects
High cholesterol levels are known to be a risk factor for heart diseases; doctors and nutritionists worldwide recommend keeping cholesterol under check via diet, exercise and other mechanisms.
Cholesterol is of two main types — high-density lipoprotein (HDL) or “good cholesterol” and low-density lipoprotein (LDL) or “bad cholesterol”.
An increase in LDL or uncontrolled LDL is considered to be a primary marker of cardiovascular disease risks. Most anti-high cholesterol therapies target the reduction of LDL cholesterol.
But what happens when you cannot control LDL cholesterol despite using every mechanism or therapy you can? This inability to control LDL levels is known as homozygous familial hypercholesterolemia.
Homozygous familial hypercholesterolemia
According to a study published in the European Heart Journal in 2014, homozygous familial hypercholesterolemia (HoFH) is a rare and life-threatening condition that is usually passed down in families, as the name suggests. The condition is characterized by a markedly elevated level of LDL cholesterol and an accelerated, premature atherosclerotic cardiovascular disease (ACVD) risk that is likely to increase early mortality risk. The study suggests that most patients with HoFH develop ACVD before the age of 20 years and generally do not survive past 30 years.
So, the primary goal of healthcare and research professionals is to prevent the onset of ACVD in HoFH patients by early and comprehensive control of the condition. Early detection of the condition and its complications is therefore as necessary as the need to optimize treatment in childhood itself so that the condition does not get any worse or progress to ACVD.
Treating hypercholesterolemia with evinacumab?
A new study presented at the American Heart Association’s Scientific Sessions 2020 suggests that an investigational drug called evinacumab may be effective in controlling LDL levels even in patients with HoFH. The study is based on the premise that HoFH is associated with genetic variations or mutations that result in virtually absent or impaired LDL-receptor activity and affects growth factors such as angiopoietin-like 3 (ANGPTL3).
Evinacumab is a monoclonal antibody (meaning it’s a man-made antibody designed by cloning a unique white blood cell) which acts against ANGPTL3 and has potential benefits for HoFH patients.
To see if this drug actually has an LDL-lowering effect, the researchers observed the effects of evinacumab on 65 patients with HoFH who were receiving stable, lipid-lowering therapy. The patients were divided into two groups, with one being given an intravenous infusion of evinacumab at a dose of 15 mg per kilogram of body weight every four weeks, while the other received a placebo. The results were measured in the form of the percentage change in LDL cholesterol levels from the beginning of the study up to the 24-week mark.
In the 24th week, patients in the group that received evinacumab had a relative reduction in their LDL cholesterol levels of 47.1 percent, while in the placebo group, the LDL levels increased by 1.9 percent. Mild side effects of evinacumab include difficulty breathing and mild anaphylactic reaction, yet this drug is well-tolerated by most patients without any severe side effects. The researchers thus concluded that the administration of evinacumab can lower LDL cholesterol levels in patients with HoFH by almost half, making it a potentially effective treatment for HoFH and a method of reducing the risk of cardiovascular disease and death among these patients.
The findings of this study are now published in The New England Journal of Medicine and the researchers are hoping evinacumab gets approved for clinical use by the US Food and Drug Administration (FDA). If approved, this drug could be used widely by cardiologists to treat rare but potentially fatal conditions like HoFH.
For more information, read our article on High cholesterol.
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