Prevention & lipidsRandomised controlled trial
Plozasiran (ARO-APOC3) for Severe Hypertriglyceridemia
- Randomised controlled trial
- phase 2b
- placebo-controlled
- double-blind
- dose-ranging
- 74 centres
- Follow-up through week 48
74 centers in US, Europe, New Zealand, Australia, Canada; May 31, 2021 to August 31, 2023
Authors' conclusion
In this randomized clinical trial of patients with sHTG, plozasiran decreased triglyceride levels, which fell below the 500 mg/dL threshold of acute pancreatitis risk in most participants.
Study context
- Population
- Adults with severe hypertriglyceridemia (fasting TG 500–4000 mg/dL) on stable lipid-lowering treatment226 in primary analysis
- Participants
- 229 adults
- Comparison
- Plozasiran vs placebo
- Primary endpoint
- Placebo-subtracted difference in mean % TG change
- Follow-up
- Week 24
Primary result
% change in TG
Placebo-adjusted least squares (LS)-mean reduction
−57 %
95% CI −71.9% to −42.1%
P < 0.001
Plozasiran 50 mg vs Placebo
placebo-adjusted LS-mean reduction −57 % (95% CI −71.9% to −42.1%); P < 0.001
As reported in the abstract
Further findings
| Outcome | Values | Estimate | P value | |
|---|---|---|---|---|
| APOC3, placebo-adjusted LS-mean % change (highest dose) · week 24 · highest dose | placebo-adjusted LS-mean reduction −77 % (95% CI −89.1% to −65.8%) | P < 0.001 | ||
| LDL-C, placebo-adjusted LS-mean % change (highest dose) · highest dose; dose-dependent increases | placebo-adjusted LS-mean increase 60 % (95% CI 31%–89%) | P < 0.001 | ||
| −100−50050100Difference, % (linear scale) |
| Outcome | Values | Estimate | P value |
|---|---|---|---|
| TG <500 mg/dL | Plozasiran 90.6% |
- TG <500 mg/dL: 144 of 159 plozasiran-treated patients
Apolipoprotein B (ApoB) and non-HDL-C
- Non-HDL-C decreased significantly at all doses; placebo-adjusted change at highest dose
- −20%
- ApoB did not increase
Remnant cholesterol, ApoB48, HDL-C · through week 48
- Significant durable reductions in remnant cholesterol and ApoB48 and increases in HDL-C
Safety
Adverse events
- Serious AEs mild to moderate, not treatment related; none led to discontinuation or death
- 0
- AE rates similar with plozasiran vs placebo
Original publication
Plozasiran (ARO-APOC3) for Severe Hypertriglyceridemia. JAMA Cardiol. Published 1 July 2024. doi:10.1001/jamacardio.2024.0959
Summarised from the published abstract; every number is checked against it