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Evinacumab in Severe Hypertriglyceridemia with or without Lipoprotein Lipase Pathway Mutations: A Phase 2 Randomized Trial

June 29, 2023

In collaboration with colleagues from other institutions, Erin Kershaw, MD, chief, UPMC Division of Endocrinology and Metabolism, and David Whitcomb, MD, PhD, professor emeritus, UPMC Division of Gastroenterology, Hepatology, and Nutrition, recently published a notable research article in Nature Medicine.

Researchers evaluated evinacumab, a medication used to lower triglycerides, across three cohorts of patients with severe hypertriglyceridemia (sHTG).

Background: sHTG is known as a risk factor for developing acute pancreatitis. It is believed that current therapeutic approaches for sHTG fail to reduce triglycerides, a type of fat lipid found in blood, and, therefore, fail to prevent acute pancreatitis.

Methods: Fifty-one patients with a history of hospitalization for acute pancreatitis were randomized 2:1 to intravenous evinacumab 15 mg kg−1 or placebo every four weeks over a 12-week double-blind treatment period. A double-blind method limits the potential for bias, since neither the participants nor the researchers knew who was receiving which treatment. The double-blind treatment was followed by a 12-week single-blind treatment period where the participants did not know whether they were assigned to the treatment or control groups. The primary end point was the mean percent reduction in triglycerides from baseline after 12 weeks of evinacumab exposure in cohort 3.

Results: While evinacumab reduced triglycerides in cohort 3 by a mean of −27.1%, the primary end point was not met.

Conclusion: There were no notable differences in adverse events between evinacumab and placebo treatment groups during the double-blind treatment period. Although the primary end point of a reduction in triglycerides did not meet the prespecified significance level, the observed safety and changes in lipid and lipoprotein levels support the further evaluation of evinacumab in larger trials of patients with sHTG.

Publication Information

Rosenson RS, Gaudet D, Ballantyne CM, Baum SJ, Bergeron J, Kershaw EE, Moriarty PM, Rubba P, Whitcomb DC, Banerjee P, Gewitz A, Gonzaga-Jauregui C, McGinniss J, Ponda MP, Pordy R, Zhao J, Rader DJ. Evinacumab in severe hypertriglyceridemia with or without lipoprotein lipase pathway mutations: a phase 2 randomized trial. Nat Med. 2023 Mar;29(3):729-737. doi: 10.1038/s41591-023-02222-w. Epub 2023 Mar 6. PMID: 36879129; PMCID: PMC10033404.

Read more about this study or view a full list of publications from the Kershaw Lab.