Lipid-efficacy RCT · J Am Coll Cardiol 2025
PURSUIT trial
An Oral PCSK9 Inhibitor for Treatment of Hypercholesterolemia: The PURSUIT Randomized Trial.
The bottom line
In statin-treated patients with hypercholesterolemia, the oral PCSK9 inhibitor AZD0780 produced robust, dose-dependent LDL-C reductions over 12 weeks with an adverse event rate similar to placebo.
Primary lipid endpoint metUS status: Investigational
At a glance
- Medicine
- AZD0780 oral once daily at 1, 3, 10, or 30 mg doses
- Compared with
- Matching placebo, oral once daily
- People
- 428
- Who took part
- Patients with hypercholesterolemia on background moderate-to-high-intensity statin treatment, fasting LDL-C ≥70 mg/dL (1.8 mmol/L) and <190 mg/dL (4.9 mmol/L), triglycerides <400 mg/dL, with or without ezetimibe at baseline; 52.1% male, average age 62.4 ± 7.6 years
- Design
- randomized, double-blind, placebo-controlled, multicenter, phase 2
- Follow-up
- 12 weeks
- Main question
- Percent change of LDL-C from baseline to week 12
Main result
Placebo-corrected difference in least squares mean percent change of LDL-C for AZD0780 1, 3, 10, and 30 mg vs placebo was -35.3% (95% CI: -43.6% to -26.9%), -37.9% (95% CI:-46.3% to -29.5%), -45.2% (95% CI: -53.5% to -36.9%), and -50.7% (95% CI: -59.0% to -42.4%), respectively
Effect on LDL cholesterol
Placebo-corrected LDL-C reduction of -35.3% to -50.7% across the 1-30 mg dose range at week 12
Other results
The proportion of patients reaching the ACC/AHA guideline LDL-C goal for high-risk patients increased in a dose-proportional manner
Safety
Adverse events compared similarly between the total AZD0780 treatment group (38.2%) and placebo (32.6%)
In the trial's own words
“At week 12, compared with baseline, the placebo-corrected difference in least squares mean percent change of LDL-C for AZD0780 1, 3, 10, and 30 mg vs placebo was -35.3% (95% CI: -43.6% to -26.9%), -37.9% (95% CI:-46.3% to -29.5%), -45.2% (95% CI: -53.5% to -36.9%), and -50.7% (95% CI: -59.0% to -42.4%), respectively.”
Quoted from the abstract of J Am Coll Cardiol 2025, checked word for word against PubMed. PubMed 40167413 · Full paper (DOI)
How this medicine works, where it stands and what it costs: AZD0780 (laroprovstat)
Common questions
What did the PURSUIT trial find?
In statin-treated patients with hypercholesterolemia, the oral PCSK9 inhibitor AZD0780 produced robust, dose-dependent LDL-C reductions over 12 weeks with an adverse event rate similar to placebo.
Who was in PURSUIT?
428 people. Patients with hypercholesterolemia on background moderate-to-high-intensity statin treatment, fasting LDL-C ≥70 mg/dL (1.8 mmol/L) and <190 mg/dL (4.9 mmol/L), triglycerides <400 mg/dL, with or without ezetimibe at baseline; 52.1% male, average age 62.4 ± 7.6 years.
What was PURSUIT's main result?
Placebo-corrected difference in least squares mean percent change of LDL-C for AZD0780 1, 3, 10, and 30 mg vs placebo was -35.3% (95% CI: -43.6% to -26.9%), -37.9% (95% CI:-46.3% to -29.5%), -45.2% (95% CI: -53.5% to -36.9%), and -50.7% (95% CI: -59.0% to -42.4%), respectively
How much did LDL cholesterol change in PURSUIT?
Placebo-corrected LDL-C reduction of -35.3% to -50.7% across the 1-30 mg dose range at week 12
Related trials
- LIBerate-HR (2024)Monthly lerodalcibep added to maximally tolerated statins substantially lowers LDL-C and helps most high-risk patients reach guideline LDL-C targets, with a safety profile similar to placebo aside from mild/moderate injection site reactions.
- CORALreef HeFH (2026)In patients with heterozygous familial hypercholesterolemia already on statin therapy, adding oral enlicitide substantially and safely lowered LDL-C and other atherogenic lipid measures compared with placebo.
- CORALreef Lipids (2026)In patients with or at risk for atherosclerotic cardiovascular disease, the oral PCSK9 inhibitor enlicitide substantially lowered LDL cholesterol and other atherogenic lipid markers compared with placebo, with adverse event rates similar between groups.
- VESALIUS-CV (2026)In patients with atherosclerosis or diabetes but no prior MI or stroke, adding evolocumab to therapy significantly lowered the risk of major cardiovascular events compared with placebo, with no apparent safety concerns.
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