Evinacumab reduces atherogenic lipoproteins in patients with refractory hyperlipidemia
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Key takeaways:
- Evinacumab provided sustained LDL reduction out to 72 weeks in patients with high cholesterol despite maximally tolerated therapy.
- It also lowered ApoB, fasting triglycerides, non-HDL and total cholesterol.
The fully monoclonal angiopoietin-like 3 antibody evinacumab conferred sustained, long-term reductions in LDL and other atherogenic lipoproteins among patients with refractory hyperlipidemia, researchers reported.
“Heterozygous familial hypercholesterolemia (HeFH) is a common yet underdiagnosed genetic disorder. More than 90% of patients with genetically confirmed HeFH have a pathogenic loss-of-function gene variation in the LDLR gene, leading to diminished or absent hepatic uptake and clearance of circulating LDL-C,” Robert S. Rosenson, MD, director of metabolism and lipids for the Mount Sinai Health System and professor of medicine in cardiology at the Icahn School of Medicine at Mount Sinai, and colleagues wrote. “Despite treatment with maximally tolerated combinations of available lipid-lowering therapies, some patients with HeFH do not achieve recommended LDL-C treatment thresholds.”
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In a previous phase 2 trial, Rosenson and colleagues randomly assigned 272 patients with refractory hypercholesterolemia despite treatment with statins and other lipid-lowering therapies to subcutaneous or IV evinacumab-dgnb (Evkeeza, Regeneron) at varying doses or placebo.
As Healio previously reported, evinacumab reduced LDL by more than 50% compared with placebo.
For the present study, Rosenson and colleagues reported their findings from the subsequent open-label treatment period of IV evinacumab 15 mg/kg every 4 weeks.
The analysis included 96 patients (mean age, 54.4 years; 54.2% women), of whom 91.7% completed the 48-week open-label treatment period and a 24-week follow-up period.
All participants had primary hypercholesterolemia — defined as HeFH or established clinical atherosclerotic CVD without FH — refractory to maximally tolerated lipid-lowering therapies.
Mean LDL at baseline was 145.9 mg/dL.
At 72 weeks, evinacumab reduced LDL by a mean of 45.5% from baseline.
Additional reductions in other atherogenic lipoproteins were observed:
- apolipoprotein B (38%);
- non-HDL (48.4%);
- total cholesterol (42.6%); and
- median fasting triglyceride (57.2%).
Overall, 81.3% of participants experienced at least one treatment-emergent adverse event, of which 9.4% were considered serious; however, all were considered unrelated to evinacumab treatment, the researchers reported.
“Results of this randomized clinical trial demonstrate that, in patients with and without HeFH and refractory hypercholesterolemia, evinacumab provided clinically meaningful and sustained reductions in LDL-C level and was generally well tolerated,” the researchers wrote. “Larger studies in a broader population would be needed to define clinical efficacy and provide more robust long-term safety data.”
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