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Evinacumab Reduces Lipids, Cholesterol in Hypercholsterolemia and Hypertriglyceridemia

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Data from a meta-analysis of evinacumab trials reveal significant reductions in cholesterol and other lipid markers among patients with dyslipidemia.

Data from an analysis of 4 major trials within the evinacumab (Evkeeza) program are shedding further light on the effects of the agent on lipid levels among patients with dyslipidemia.

Conducted by Muhammad Saqlain Mustafa, MBBS, of the Aga Khan University Hospital, and colleagues, results of the study demonstrate use of evinacumab in patient populations with hypercholesterolemia and hypertriglyceridemia was associated with significant reductions cholesterol and other lipid markers, with a tolerability profile study investigators considered favorable.1

The first FDA-approved angiopoietin-like 3 (ANGPTL3) inhibitor, evinacumab received approval from the US Food and Drug Administration in February 2021 as an adjunct to other low-density lipoprotein cholesterol (LDL-C) lowering therapies to treat adult and pediatric patients aged 12 years and older with homozygous familial hypercholesterolemia (HoFH) based on data from the phase 3 ELPISE-HoFH trial. A subsequent approval in March 2023 expanded the agent’s indication to include patients aged 5 to 11 years with HoFH.2,3

In the current study, Mustafa and colleagues sought to provide an overview of the effects of evinacumab among patient populations with hypercholesterolemia and hypertriglyceridemia through a systematic review and meta-analysis of randomized controlled trials. The primary outcomes of interest for the study were the standard mean difference (SMD) observed for change in triacylglycerols, total cholesterol, high-density lipoprotein cholesterol (HDL-C), LDL-C, apolipoprotein (Apo) B, and Apo C3.1

For inclusion in the systematic review and meta-analysis, studies were required to compare evinacumab, at doses of 5 or 15 mg, to placebo with outcomes of interest related to lipid levels and adverse events. A search of relevant databases identified 4 randomized controlled trials with a total population of 270 patients for inclusion in the analysis.1

Upon analysis, significant reductions were observed for (SMD, −6.09, 95% confidence interval [CI], −14.53 to 2.36; P = .16), total cholesterol (SMD, −6.20; 95% CI, −11.53 to −0.88; P = .02), LDL-C (SMD, −4.58; 95% CI, −9.13 to −0.03, P = .05), ApoB (SMD, −4.01; 95% CI, −7.53 to −0.46; P = .03), and Apo C3 (SMD, −7.67; 95% CI, −12.94 to −2.41; P = .004). Investigators pointed out a decrease in HDL-C was also observed in their analyses (SMD, −0.79; 95% CI, −1.27 to −0.31; P = .001). Analysis of evinacumab’s safety profile demonstrated there were no significant associations with any adverse events, which investigators suggest was indicative of favorable tolerability.1

“Further research is warranted to comprehensively assess its safety and clinical effectiveness, emphasizing the need for additional data to support its use in managing cardiovascular disease,” wrote investigators.1

The study from Mustafa and colleagues supports the findings of a recent study from Robert Rosenson, MD, director of Cardiometabolic Disorders at Icahn School of Medicine at Mount Sinai. The study, which was published in March 2024, assessed the effects of evinacumab use on triglyceride levels using dating from 3 randomized controlled trials.4

The study’s primary outcome of interest was change in triglyceride-rich lipoprotein levels from baseline to 12, 16, or 24 weeks for the phase 2 hypertriglyceridemia trial, the phase 2 refractory hypercholesterolemia trial, and the phase 3 ELIPSE trial, respectively. Results indicated reductions in mean triglyceride-rich lipoprotein levels were observed in all evinacumab treatment arms, with reductions of 50% or greater from baseline observed at the greatest doses. Results also indicated levels of non-HDL-C and HDL-C were reduced from baseline among evinacumab-treated patients in all 3 trials.4

References:

  1. Rangwala HS, Fatima H, Ali M, et al. Evaluating the Effectiveness and Safety of Evinacumab in Treating Hypercholesterolemia and Hypertriglyceridemia: A Systematic Review and Meta-analysis of Randomized Controlled Trials. Am J Cardiovasc Drugs. Published online May 7, 2024. doi:10.1007/s40256-024-00649-1
  2. FDA Center for Drug Evaluation and Research. FDA approves add-on therapy for patients with genetic form of severely. U.S. Food and Drug Administration. February 11, 2021. Accessed May 16, 2024. https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-add-therapy-patients-genetic-form-severely-high-cholesterol-0.
  3. Regeneron Pharmaceuticals Inc. FDA approves first-in-class Evkeeza® (evinacumab-dgnb) for young children with ultra-rare form of high cholesterol. Regeneron Pharmaceuticals Inc. March 22, 2023. Accessed May 16, 2024. https://investor.regeneron.com/news-releases/news-release-details/fda-approves-first-class-evkeezar-evinacumab-dgnb-young-children.
  4. Campbell P. Clinical trials analysis finds evinacumab could reduce triglyceride-rich lipoprotein. HCP Live. March 21, 2024. Accessed May 16, 2024. https://www.hcplive.com/view/clinical-trials-analysis-finds-evinacumab-reduces-triglyceride-rich-lipoprotein.
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