laroprovstat (AZD0780) / AstraZeneca - LARVOL DELTA

Oral PCSK9 inhibitors: closing the gap between potency and practicality. (PubMed, Curr Opin Lipidol) - "Oral PCSK9 inhibitors have the potential to improve the convenience and acceptability of PCSK9-targeted therapy. Whether these advantages translate into greater real-world uptake will depend on affordability, payer coverage, clinician adoption, and long-term adherence."

Journal • Cardiovascular

A Phase III Study to Assess the Effect of FDC Laroprovstat/Rosuvastatin Compared With Laroprovstat, Rosuvastatin and Placebo on LDL-C in LLT-naïve Patients. (clinicaltrials.gov) - P3 | N=600 | Recruiting | Sponsor: AstraZeneca | Not yet recruiting ➔ Recruiting

Enrollment open • Dyslipidemia

Laroprovstat, an Oral Small Molecule PCSK9 Inhibitor Demonstrates Improvements in the Lipoprotein Profile in Patients with Hypercholesterolemia (AHA 2026) - "Abstract is embargoed at this time."

Clinical • Dyslipidemia • Metabolic Disorders

Design and baseline data of AZURE-HeFH, a phase 3 study assessing the effect of the oral PCSK9 inhibitor laroprovstat on LDL cholesterol in patients with heterozygous familial hypercholesterolaemia (ESC 2026) - "Ezetimibe was used by 73.1% of participants. Based on preliminary data, 472 participants were randomised and dosed between June and December 2025. Baseline characteristics are shown in the Table. Approximately 21% had a prior ASCVD event."

Clinical • P3 data • Atherosclerosis • Cardiovascular • Dyslipidemia

Design and baseline data of AZURE-LDL, a phase 3 study assessing the effect of the oral PCSK9 inhibitor laroprovstat on LDL cholesterol in patients with, or at risk for, ASCVD (ESC 2026) - " AZURE-LDL is a fully enrolled, Phase 3, randomised, double-blind, placebo-controlled trial in participants ≥18 years with either a prior ASCVD event and LDLc ≥1.4 mmol/L, or at high cardiovascular risk without a prior ASCVD event and with LDLc ≥1.8 mmol/L; all on maximally tolerated statin therapy, with or without ezetimibe or bempedoic acid (Figure). Based on preliminary data, 3053 participants were randomised and dosed between June and December 2025. Baseline characteristics are shown in the Table. The cohort comprises participants with a prior ASCVD event (59.4%) or those at high risk of experiencing a first ASCVD event."

Clinical • P3 data • Atherosclerosis • Cardiovascular

A Study to Assess the Effect of AZD0780 on the Pharmacokinetics of AZD4954 and Vice Versa in Healthy Adults (clinicaltrials.gov) - P1 | N=31 | Completed | Sponsor: AstraZeneca | Recruiting ➔ Completed

Trial completion

A Phase I, Cross-over Study Comparing the Relative Bioavailability of Laroprovstat Plus Ezetimibe Fixed Combination Drug Products Versus Their Single Therapy Products in Healthy Adults (clinicaltrials.gov) - P1 | N=18 | Active, not recruiting | Sponsor: AstraZeneca | Recruiting ➔ Active, not recruiting

Enrollment closed

A Study to Investigate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics With AZD0780 Following Repeated Dose Administration in Healthy Adults With Elevated LDL-C Levels (clinicaltrials.gov) - P1 | N=40 | Completed | Sponsor: AstraZeneca | Active, not recruiting ➔ Completed

Trial completion

AZURE-Outcomes: A Phase III Study of AZD0780 on Major Adverse CV Events in Patients With a History of ASCVD Events or at High Risk for a First Event (clinicaltrials.gov) - P3 | N=15100 | Recruiting | Sponsor: AstraZeneca | -> Recruiting

Adverse events • Enrollment open • Atherosclerosis • Cardiovascular

A Phase I Study Comparing the Relative Bioavailability of a Fixed-Dose Combination of Laroprovstat/Rosuvastatin vs Their Single Therapy Products in Healthy Adults (clinicaltrials.gov) - P1 | N=44 | Completed | Sponsor: AstraZeneca | Active, not recruiting ➔ Completed

Trial completion

A Phase I, Cross-over Study Comparing the Relative Bioavailability of Laroprovstat Plus Ezetimibe Fixed Combination Drug Products Versus Their Single Therapy Products in Healthy Adults (clinicaltrials.gov) - P1 | N=18 | Recruiting | Sponsor: AstraZeneca | Not yet recruiting ➔ Recruiting

Enrollment open

Meta-Analysis of Oral PCSK9 Inhibitors for Hypercholesterolemia in Adults: A Systematic Review and GRADE Assessment. (PubMed, Cardiol Rev) - "Five trials (n = 4232) evaluating AZD0780, NNC0385-0434, MK-0616, and enlicitide were included. No significant differences were observed in discontinuation due to adverse events, any adverse events, serious adverse events, or treatment-related adverse events. Oral PCSK9 inhibitors provide substantial short-term reductions in atherogenic lipoproteins without an apparent excess of short-term adverse events; longer-term cardiovascular outcome trials are needed."

Journal • Retrospective data • Cardiovascular • Dyslipidemia • Metabolic Disorders • APOB

A Phase I, Cross-over Study Comparing the Relative Bioavailability of Laroprovstat Plus Ezetimibe Fixed Combination Drug Products Versus Their Single Therapy Products in Healthy Adults (clinicaltrials.gov) - P1 | N=18 | Not yet recruiting | Sponsor: AstraZeneca

New P1 trial

LAZURE: A Study to Investigate the Effect of AZD0780 Tablets in Combination With Rosuvastatin Tablets on Low Density Lipoprotein Cholesterol Levels (LDL-C) in Adult Participants With Dyslipidaemia (clinicaltrials.gov) - P2 | N=76 | Active, not recruiting | Sponsor: AstraZeneca | Recruiting ➔ Active, not recruiting

Enrollment closed • Dyslipidemia

A Phase III Study to Assess the Effect of FDC Laroprovstat/Rosuvastatin Compared With Laroprovstat, Rosuvastatin and Placebo on LDL-C in LLT-naïve Patients. (clinicaltrials.gov) - P3 | N=600 | Not yet recruiting | Sponsor: AstraZeneca

New P3 trial • Dyslipidemia

A Phase III Study to Assess the Effect of FDC Laroprovstat/Rosuvastatin Compared With Rosuvastatin on LDL-C in Patients With Hypercholesterolaemia (clinicaltrials.gov) - P3 | N=200 | Not yet recruiting | Sponsor: AstraZeneca

New P3 trial • Dyslipidemia

Efficacy and Safety of Oral PCSK9 Inhibitors: Insights from a Meta-analysis of RCTS. (PubMed, Eur J Prev Cardiol) - "Oral PCSK9 inhibitors demonstrate potent LDL-C-lowering efficacy, comparable to parenteral PCSK9i, with favourable effects on other atherogenic lipids and a reassuring short-term safety profile."

Journal • Retrospective data • Dyslipidemia • Metabolic Disorders • APOB

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-Naive Patients. (PubMed, Circulation) - P1 | "In treatment-naive participants with hypercholesterolemia, combined rosuvastatin 20 mg and laroprovstat 30 mg treatment led to an 80% LDL-C reduction, supporting further development of laroprovstat as the first oral small-molecule PCSK9 inhibitor in patients with hypercholesterolemia. URL: https://www.clinicaltrials.gov; Unique identifier: NCT05384262."

Journal • P1 data • Cardiovascular • Dyslipidemia • Familial Hypercholesterolemia • Genetic Disorders • Heterozygous Familial Hypercholesterolemia • Metabolic Disorders • PCSK9 • STAT3

PCSK9 inhibitors: an updated patent review 2024-2025. (PubMed, Expert Opin Ther Pat) - "The clinical development of small-molecule PCSK9 inhibitors, such as MK-0616 (enlicitide) and AZD0780 (laroprovstat), demonstrates that PCSK9 is still a drug target of great interest for both academic and pharmaceutical companies. The numerous patents deposited in the last two years cover compounds that are structurally related to previously deposited general structures as well as newly developed scaffolds that include quinolines and isoquinolines, peptides, pyridine, and benzothiazole derivatives. However, with mAbs and siRNAs dominating the market, small molecules are required to prove superior cost-efficiency, combination value, and cardiovascular advantages that extend beyond LDL-C reduction."

Journal • Review • Cardiovascular • Dyslipidemia • Metabolic Disorders

A Phase I Study Comparing the Relative Bioavailability of a Fixed-Dose Combination of Laroprovstat/Rosuvastatin vs Their Single Therapy Products in Healthy Adults (clinicaltrials.gov) - P1 | N=44 | Active, not recruiting | Sponsor: AstraZeneca | Recruiting ➔ Active, not recruiting

Enrollment closed

A Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of AZD0780 in Participants With Dyslipidaemia (clinicaltrials.gov) - P2/3 | N=432 | Active, not recruiting | Sponsor: AstraZeneca | Recruiting ➔ Active, not recruiting

Enrollment closed • Dyslipidemia

New frontiers in the treatment of hypercholesterolaemia: oral inhibition of PCSK9. (PubMed, Eur Heart J Suppl) - "Agents in advanced development include enlicitide (MK-0616) and laroprovstat (AZD0780), while DC371739, NNC0385-0434 (development currently suspended), and CVI-LM001 should also be considered...AZD0780 demonstrates dose-dependent reductions in LDL-C (up to 50%) and potential synergism with rosuvastatin, whereas NNC0385-0434-despite documenting significant decreases in LDL-C and Lp(a)-has been discontinued. DC371739 (a dual PCSK9/ANGPTL3 inhibitor) and CVI-LM001 (a transcriptional modulator) may represent additional therapeutic perspectives. Overall, oral PCSK9 inhibitors show consistent efficacy and favourable safety profiles, positioning them as next-generation lipid-lowering therapies, pending cardiovascular outcome data from ongoing studies."

Journal • Cardiovascular • Dyslipidemia • Heterozygous Familial Hypercholesterolemia • ANGPTL3 • APOB

A Study to Investigate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics With AZD0780 Following Repeated Dose Administration in Healthy Adults With Elevated LDL-C Levels (clinicaltrials.gov) - P1 | N=40 | Active, not recruiting | Sponsor: AstraZeneca | Recruiting ➔ Active, not recruiting

Enrollment closed

A Study to Assess the Effect of AZD0780 on the Pharmacokinetics of AZD4954 and Vice Versa in Healthy Adults (clinicaltrials.gov) - P1 | N=32 | Recruiting | Sponsor: AstraZeneca | Not yet recruiting ➔ Recruiting

Enrollment open

A Study to Assess the Effect of AZD0780 on the Pharmacokinetics of AZD4954 and Vice Versa in Healthy Adults (clinicaltrials.gov) - P1 | N=32 | Not yet recruiting | Sponsor: AstraZeneca

New P1 trial