laroprovstat (AZD0780) / AstraZeneca - LARVOL DELTA

A Study to Investigate the Effect of AZD0780 on Metformin Pharmacokinetics in Healthy Adult Volunteers Aged 18 to 55 Years (clinicaltrials.gov) - P1 | N=14 | Recruiting | Sponsor: AstraZeneca | Not yet recruiting ➔ Recruiting

Enrollment open

Lipid-Lowering Efficacy and Safety of Oral Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors: A Systematic Review and Meta-Analysis. (PubMed, Adv Ther) - "Oral PCSK9 inhibitors demonstrate lipid-lowering efficacy and safety comparable to that of currently approved injectable PCSK9 therapies. These findings support their potential as a convenient and effective alternative, although current evidence remains limited to early-phase studies."

Clinical • Journal • Retrospective data • Dyslipidemia • APOB

A Study to Investigate the Pharmacokinetics, Safety, Tolerability, and Efficacy of AZD0780 With Ezetimibe Combinations in Healthy Adults With Elevated LDL-C. (clinicaltrials.gov) - P1 | N=81 | Completed | Sponsor: AstraZeneca | Active, not recruiting ➔ Completed

Trial completion • Dyslipidemia • Metabolic Disorders • APOB

Oral PCSK9 Inhibitors for Hypercholesterolemia: A Systematic Review and Meta-Analysis of Randomized Trials (AHA 2025) - "MK-0616 achieved the greatest LDL-C reduction (–53.69%; 95% CI, –61.05% to –46.34%), followed by NNC0385-0434 (–46.23%; 95% CI, –63.15% to –29.31%) and AZD0780 (–38.18%; 95% CI, –45.06% to –31.29%). Oral PCSK9 inhibitors significantly reduced LDL-C, lipoprotein(a), apolipoprotein B, and total cholesterol compared to placebo, with no significant reduction in triglycerides. Among the agents studied, MK-0616 demonstrated the greatest overall LDL-C lowering effect."

Retrospective data • Review • Dyslipidemia • Metabolic Disorders • APOB

Model-Based Evaluation of LDL-C Lowering for Laroprovstat (AZD0780), An Oral Small Molecule PCSK9 Inhibitor, and Rosuvastatin (AHA 2025) - P2 | "The modeling analyses demonstrate superior efficacy of combination therapy with laroprovstat and rosuvastatin across the therapeutic range of rosuvastatin. There is no need for dose adjustment of laroprovstat. The findings support a co-formulation with a statin to achieve guideline-directed LDL-C goals in patients not reaching target LDL-C levels with statins alone, providing a convenient, a once daily oral option."

Atherosclerosis • STAT3

Laroprovstat (AZD0780) an oral, small molecule PCSK9 inhibitor demonstrates improvements in the lipid profile in participants with hypercholesterolemia: Results from a Phase 1 study (AHA 2025) - P1 | "In treatment-naïve hypercholesterolemic patients, rosuvastatin combined with laroprovstat led to nearly 80% LDL-C reduction and was well-tolerated in this Phase 1 study. These data support further development of laroprovstat as the first oral small molecule PCSK9 inhibitor."

P1 data • Dyslipidemia • Metabolic Disorders • APOB • APOE • STAT3

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 | Not yet recruiting | Sponsor: AstraZeneca

New P2 trial • Dyslipidemia

A Study to Investigate the Effect of AZD0780 on Metformin Pharmacokinetics in Healthy Adult Volunteers Aged 18 to 55 Years (clinicaltrials.gov) - P1 | N=14 | Not yet recruiting | Sponsor: AstraZeneca

New P1 trial

A Study to Investigate the Pharmacokinetics, Safety, Tolerability, and Efficacy of AZD0780 With Ezetimibe Combinations in Healthy Adults With Elevated LDL-C. (clinicaltrials.gov) - P1 | N=81 | Active, not recruiting | Sponsor: AstraZeneca | Recruiting ➔ Active, not recruiting | N=120 ➔ 81

Enrollment change • Enrollment closed • Dyslipidemia • Metabolic Disorders • APOB

AZD0780, a novel, oral PCSK9 inhibitor with properties allowing for broad use, food-intake independency and co-administration with other lipid lowering therapies (ESC-WCC 2025) - "Population PK modeling explored predictors of AZD0780 exposure, including demographics, ezetimibe concomitant use, and statin-intensity. The PK and ADME properties of AZD0780 suggest it can be widely used without dose adjustment across patient subpopulations, including those with co-morbidities such as renal impairment or obesity. AZD0780 may offer a convenient once-daily oral therapy that could be co-administered with other oral lipid lowering treatments, such as statins, to help a large majority of patients reach guideline recommended LDL-C goals."

Acute Coronary Syndrome • Cardiovascular

AstraZeneca plans to invest $50 billion in America for medicines manufacturing and R&D (AstraZeneca Press Release) - "AstraZeneca today announces $50 billion of investment in the United States by 2030, building on America’s global leadership in medicines manufacturing and R&D. This investment is expected to create tens of thousands of new, highly skilled direct and indirect jobs across the country powering growth and delivering next generation medicines for patients in America and worldwide. The cornerstone of this landmark investment is a new multi-billion dollar US manufacturing facility that will produce drug substances for the Company’s innovative weight management and metabolic portfolio, including oral GLP-1, baxdrostat, oral PCSK9 and combination small molecule products. The new state-of-the-art centre will produce small molecules, peptides and oligonucleotides. This multi-billion dollar capital investment is in addition to the $3.5 billion announced in November 2024."

Commercial • Metabolic Disorders • Obesity

AZURE-HeFH: A Phase III Study to Assess the Effect of AZD0780 on LDL-C in Patients With HeFH (clinicaltrials.gov) - P3 | N=405 | Recruiting | Sponsor: AstraZeneca | Not yet recruiting ➔ Recruiting

Enrollment open • Dyslipidemia • Familial Hypercholesterolemia • Heterozygous Familial Hypercholesterolemia

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 | Not yet recruiting ➔ Recruiting

Adverse events • Enrollment open • Atherosclerosis • Cardiovascular

AZURE-LDL: A Phase III Study to Assess the Effect of AZD0780 on LDL-C in Patients With Clinical ASCVD or at Risk for a First ASCVD Event (clinicaltrials.gov) - P3 | N=2800 | Recruiting | Sponsor: AstraZeneca | Not yet recruiting ➔ Recruiting

Enrollment open • Atherosclerosis • Cardiovascular • Dyslipidemia

AZURE-LDL: A Phase III Study to Assess the Effect of AZD0780 on LDL-C in Patients With Clinical ASCVD or at Risk for a First ASCVD Event (clinicaltrials.gov) - P3 | N=2800 | Not yet recruiting | Sponsor: AstraZeneca

New P3 trial • Atherosclerosis • Cardiovascular • Dyslipidemia

AZURE-HeFH: A Phase III Study to Assess the Effect of AZD0780 on LDL-C in Patients With HeFH (clinicaltrials.gov) - P3 | N=405 | Not yet recruiting | Sponsor: AstraZeneca

New P3 trial • Dyslipidemia • Familial Hypercholesterolemia • Heterozygous Familial Hypercholesterolemia

A Study to Investigate the Pharmacokinetics, Safety, Tolerability, and Efficacy of AZD0780 With Ezetimibe Combinations in Healthy Adults With Elevated LDL-C. (clinicaltrials.gov) - P1 | N=120 | Recruiting | Sponsor: AstraZeneca | Trial completion date: Dec 2025 ➔ Aug 2025 | Trial primary completion date: Dec 2025 ➔ Aug 2025

Trial completion date • Trial primary completion date • Dyslipidemia • Metabolic Disorders • APOB

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 | Not yet recruiting | Sponsor: AstraZeneca

Adverse events • New P3 trial • Atherosclerosis • Cardiovascular

AZD0780-ABPM: A Study to Assess the Effect of AZD0780 on Ambulatory Blood Pressure (clinicaltrials.gov) - P2 | N=202 | Completed | Sponsor: AstraZeneca | Active, not recruiting ➔ Completed

Trial completion • Atherosclerosis • Cardiovascular • Dyslipidemia

Oral and Non-Oral Cholesterol-Lowering Drugs with PCSK9 and Other Biomolecules as Targets: Present Status and Future Prospects. (PubMed, Biomolecules) - "This review provides an overview of the existing cholesterol-lowering drugs, and the progress made so far with oral-based PCSK9 drugs for lowering LDL-cholesterol. The review is presented in several sections highlighting the molecular targets, the individual drugs, and the modes of administration, with a focus on the oral route."

Journal • Review • Cardiovascular • Dyslipidemia • Pain

Oral PCSK9 Inhibitors: Will They Work? (PubMed, Curr Atheroscler Rep) - "Enlicitide decanoate (formerly known as MK-0616) has been shown to significantly reduce LDL-C levels by a maximum of 66% from baseline with a good safety and tolerability profile...AZD0780 is another oral small molecule that lowers LDL-C levels by 52% and can be administered on top of a statin...If the results of the outcome studies will be positive, we will have a safe, effective and easy-to-use oral therapy. Oral PCSK9 inhibitors could provide a convenient alternative to injectable PCSK9 inhibitors and result in a greater number of patients receiving an effective LDL-C-lowering therapy."

Journal • Review • Atherosclerosis • Cardiovascular • Dyslipidemia

D7960C00011: An Open-label Study in Healthy Participants to Evaluate AZD0780 as an Object or Precipitant of CYP3A4-mediated Drug-drug Interactions (clinicaltrials.gov) - P1 | N=59 | Completed | Sponsor: AstraZeneca | Recruiting ➔ Completed

Trial completion • Dyslipidemia

Efficacy And Safety Of Azd0780, An Oral Small Molecule Pcsk9 Inhibitor For Treatment Of Hypercholesterolemia: Results From A Ph2b Randomized Placebo-controlled Clinical Trial - Michael J. Koren (ACC 2025) - No abstract available

Clinical • Late-breaking abstract • P2b data • Dyslipidemia • Metabolic Disorders

A Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of AZD0780 in Participants With Dyslipidaemia (clinicaltrials.gov) - P2/3 | N=300 | Recruiting | Sponsor: AstraZeneca | N=60 ➔ 300 | Trial completion date: Jun 2025 ➔ Jun 2027 | Trial primary completion date: Jun 2025 ➔ Jun 2027

Enrollment change • Trial completion date • Trial primary completion date • Dyslipidemia

An Oral PCSK9 Inhibitor for Treatment of Hypercholesterolemia: The PURSUIT Randomized Trial. (PubMed, J Am Coll Cardiol) - P2 | "AZD0780 demonstrated robust, dose-dependent reductions in LDL-C with a favorable safety and tolerability profile supporting further development of this once daily, oral treatment. (A Study to Assess the Efficacy, Safety and Tolerability of Different Doses of AZD0780 in Patients With Dyslipidemia [PURSUIT]; NCT06173570)."

Clinical • Journal • Cardiovascular • Dyslipidemia • Metabolic Disorders