Prevention & lipidsRandomised controlled trial
Laroprovstat, the First Oral Small-Molecule PCSK9 Inhibitor for the Treatment of Hypercholesterolemia: Results From a Randomized, Single-Blind, Placebo-Controlled Phase 1 Trial in Treatment-Naïve Patients
- Randomised controlled trial
- single-blind
- placebo-controlled
- phase 1
Authors' conclusion
Laroprovstat was well tolerated with no safety findings of concern and may be dosed with or without food. In treatment-naïve participants with hypercholesterolemia, combined rosuvastatin 20 mg and laroprovstat 30 mg treatment led to an 80% LDL-C reduction
Study context
- Population
- Participants with LDL-C ≥100 and ≤190 mg/dL (treatment-naïve hypercholesterolemia); single ascending doses in healthy participants with LDL-C ≥70 and ≤190 mg/dL
- Comparison
- Laroprovstat 1 mg or 30 mg vs placebo once daily for 28 days after rosuvastatin 20 mg run-in
Primary result
As reported in the abstract
LDL-C reduction vs baseline after rosuvastatin 20 mg 3-week run-in
| Outcome | Laroprovstat 1 mg | Laroprovstat 30 mg | Placebo |
|---|---|---|---|
| LDL-C reduction vs baseline after rosuvastatin 20 mg 3-week run-in | 29% (95% CI 18%–38%) | 51% (95% CI 44%–58%) | |
| Total LDL-C reduction with rosuvastatin (approximate) | 70% | 80% | Not reported in the abstract |
Further findings
| Outcome | Cmax geometric mean reduction (90% CI) | |
|---|---|---|
| Food effect (high-fat meal vs fasted) — High-fat meal vs Fasted | 1.06 (1.00–1.13) | |
| −0.500.511.5Difference (linear scale) |
| Outcome | AUCinf geometric mean reduction (90% CI) |
|---|---|
| Food effect (high-fat meal vs fasted) — High-fat meal vs Fasted | 1.15 (1.11–1.19) |
Pharmacokinetics
- Dose-proportional PK; half-life suitable for once-daily dosing
- ≈40 hours
Food effect (high-fat meal vs fasted)
- No clinically meaningful change in exposure
Preclinical (mice expressing human PCSK9)
- Increased low-density lipoprotein (LDL) receptor expression and reduced LDL-C
Original publication
Laroprovstat, the First Oral Small-Molecule PCSK9 Inhibitor for the Treatment of Hypercholesterolemia: Results From a Randomized, Single-Blind, Placebo-Controlled Phase 1 Trial in Treatment-Naïve Patients. Circulation. Published 15 May 2026. doi:10.1161/circulationaha.125.075973
Summarised from the published abstract; every number is checked against it