Oral Muvalaplin for Lowering of Lipoprotein(a)): A Randomized Clinical Trial

JAMAPublished 21 Jan 2025Randomised controlled trial

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Authors' conclusion

Muvalaplin reduced lipoprotein(a) measured using intact lipoprotein(a) and apolipoprotein(a)-based assays and was well tolerated.

Study context

Population: Lipoprotein(a) ≥175 nmol/L with atherosclerotic CVD, DM or familial hypercholesterolemia; 43 sites in Asia, Europe, Australia, Brazil and the US, 2022–2023
Participants: 233 participants

Comparison: Oral muvalaplin vs placebo
10 mg/dn = 34
60 mg/dn = 64
240 mg/dn = 68
Placebon = 67reference
Primary endpoint: Placebo-adjusted percentage change from baseline in lipoprotein(a) molar concentration (intact lipoprotein(a) assay and apolipoprotein(a)-based assay)
Follow-up: Week 12

Methodological detailsphase 2, placebo-controlled, double-blind, 43 sites

As reported in the abstract

Placebo-adjusted reduction in lipoprotein(a)

Placebo-adjusted reduction, %

10 mg/d · intact lipoprotein(a) assay: 47.6 (95% CI 35.1%–57.7%)
60 mg/d · intact lipoprotein(a) assay: 81.7 (95% CI 78.1%–84.6%)
240 mg/d · intact lipoprotein(a) assay: 85.8 (95% CI 83.1%–88.0%)
10 mg/d · apolipoprotein(a)-based assay: 40.4 (95% CI 28.3%–50.5%)
60 mg/d · apolipoprotein(a)-based assay: 70.0 (95% CI 65.0%–74.2%)
240 mg/d · apolipoprotein(a)-based assay: 68.9 (95% CI 63.8%–73.3%)

Outcome	Reduction (%) (95% CI)
Apolipoprotein B (reduction)10 mg/d vs Placebo · dose-dependent	8.9 (−2.2% to 18.8%)
Apolipoprotein B (reduction)60 mg/d vs Placebo · dose-dependent	13.1 (4.4%–20.9%)
Apolipoprotein B (reduction)240 mg/d vs Placebo · dose-dependent	16.1 (7.8%–23.7%)

High-sensitivity C-reactive protein

Oral Muvalaplin for Lowering of Lipoprotein(a)): A Randomized Clinical Trial. JAMA. Published 21 January 2025. doi:10.1001/jama.2024.24017

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