Investigational RNAi Agent Cuts Triglyceride Levels in Patients with Mixed Hyperlipidemia: Daily Dose

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Patient Care brings primary care clinicians a lot of medical news every day—it’s easy to miss an important study. The Daily Dose provides a concise summary of one of the website's leading stories you may not have seen.

On May 28, 2024, we reported on findings from a study presented at the European Atherosclerosis Society 92nd Congress and published simultaneously in the New England Journal of Medicine that examined the safety and efficacy of plozasiran, an investigational RNA interference (RNAi) therapeutic, in patients with mixed hyperlipidemia.

The study

Researchers conducted the 48-week, phase 2b, double-blind, randomized, placebo-controlled MUIR study among a total of 353 participants with mixed hyperlipidemia, defined as fasting triglyceride levels between 150-499 mg/dL and either LDL-cholesterol (LDL-C) ≥70 mg/dL or non-HDL-C >100 mg/dL. Participants were randomly assigned in a 3:1 ratio to receive 10, 25, or 50 mg plozasiran or placebo on day 1 and at week 12 (quarterly doses) or 50 mg plozasiran or placebo on day 1 and week 24 (semi-yearly dose).

The study’s primary endpoint was mean percent change in fasting triglyceride levels at week 24.

The findings

At week 24, researchers reported significant reductions in fasting triglyceride levels with plozasiran, with differences, vs placebo, in least-squares mean (LSM) percent change from baseline of –49.8%, –56%, and –62% with the the 10-, 25-, and 50-mg doses, respectively (P <.001 for all).

The investigators also found at week 24 that the majority of participants assigned to treatment with plozasiran reached normalized fasting triglyceride levels (<150 mg/dL), from 79% in the 10-mg group to 92% in the 50-mg quarterly groups and 77% in the 50-mg half-yearly group.

Authors' comment

“The promising results from treatment with plozasiran in the MUIR study help to lay the groundwork for a more extensive study to potentially test whether plozasiran reduces ASCVD risk.”

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