Plozasiran was associated with favourable changes to the number and size of triglyceride-rich lipoprotein particles (TRL-P) in the Phase 2 SHASTA-2 and MUIR studies in patients with severe hypertriglyceridaemia and mixed hyperlipidaemia respectively.
Nuclear magnetic resonance was used to determine lipoprotein particle concentration and sub class distribution. This showed that there were dose dependent, placebo-adjusted total TRL-P reductions of -46% with plozasiran in SHASTA-2, with reductions across all TRL sub classes. While total LDL-P was unchanged, large LDL-P concentration increased by +53% and medium by +56%; small LDL-P trended lower (-13%). Total HDL-P increased by +8%, primarily driven by a +36% increase in large high-density lipoprotein particles (HDL-P).
In MUIR, there were also dose-dependent reductions in TRL-P with plozasiran, including a significant reduction in total TRL-P of -48% with pooled plozasiran, and reductions across all TRL sub classes. Again, total LDL-P was unchanged, but large and medium LDL-P levels increased by +88% and +46%, respectively; small LDL-P levels decreased by -28%. Total HDL-P increased by +12%, largely due to a +83% increase in large HDL-P.
Professor Christie Ballantyne (pictured), Baylor College of Medicine, Houston, USA and co-investigators, concluded that plozasiran showed potentially favourable quantitative and qualitative changes in lipoproteins in patients with hypertriglyceridaemia and mixed hyperlipidaemia.
“The ∼50% reduction in TRL-P with no increase in apoB and possibly beneficial qualitative changes in LDL suggests the potential of plozasiran to lower cardiovascular risk, which may be evaluated in a prospective outcomes trial,” they said.
Reference
Ballantyne CM, Gaudet D, Rosenson RS et al. Effect of Targeting apoC-III with Plozasiran on Lipoprotein Particle Size and Number in Hypertriglyceridemia. J Am Coll Cardiol. 2025 Mar 12:S0735-1097(25)05892-9
