AZD0780 / AstraZeneca - LARVOL DELTA

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) - No abstract available

Acute Coronary Syndrome • Cardiovascular

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

AZD0780, a novel oral PCSK9 inhibitor, demonstrated significant LDL cholesterol (LDL-C) reduction in PURSUIT Phase IIb trial (AstraZeneca Press Release) - P2b | N=428 | PURSUIT (NCT06173570) | Sponsor: AstraZeneca | "Positive results from the PURSUIT Phase IIb trial for AstraZeneca’s AZD0780 demonstrated a statistically significant low-density lipoprotein cholesterol (LDL-C) reduction when administered on top of standard-of-care statin therapy, as compared with placebo...At 12 weeks, AZD0780 30mg taken once-daily (when added to the standard-of-care statin therapy and administered without any fasting or food restrictions) led to a 50.7% reduction in LDL-C [95% CI: -59.0%, -42.4%, p<0.001]. Similar efficacy was observed regardless of whether trial participants received moderate- or high-intensity statin doses at baseline.1,2 In addition, AZD0780 30mg enabled 84% [95%CI: 74.4%-90.7%] of trial participants to meet their American Heart Association/American College of Cardiology guideline-recommended LDL-C target (<70 mg/dL), compared to 13% [95%CI: 7.2%-22.3%] of participants on background statin therapy alone."

P2 data • 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=78 | Recruiting | Sponsor: AstraZeneca | N=42 ➔ 78

Enrollment change • Dyslipidemia

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

Enrollment closed • Atherosclerosis • Cardiovascular • Dyslipidemia

A Phase I Study to Investigate the Effect of Renal Impairment on the Pharmacokinetics, Safety, and Tolerability of AZD0780 (clinicaltrials.gov) - P1 | N=30 | Completed | Sponsor: AstraZeneca | Recruiting ➔ Completed

Trial completion • Renal Disease

A Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of AZD0780 in Participants With Dyslipidaemia (clinicaltrials.gov) - P2/3 | N=60 | Recruiting | Sponsor: AstraZeneca

New P2/3 trial • Dyslipidemia

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 | N=48 ➔ 120

Enrollment change • Dyslipidemia • Metabolic Disorders

Study to Investigate the Effect of Hepatic Impairment on the Pharmacokinetics, Safety, and Tolerability of AZD0780 (clinicaltrials.gov) - P1 | N=17 | Completed | Sponsor: AstraZeneca | Recruiting ➔ Completed | N=32 ➔ 17

Enrollment change • Trial completion • Hepatology

Emerging oral therapeutic strategies for inhibiting PCSK9. (PubMed, Atheroscler Plus) - "Subcutaneous administration of monoclonal antibodies (evolocumab and alirocumab) every 2 or 4 weeks determined a 60 % reduction of LDL cholesterol levels, while the GalNac-siRNA anti PCSK9 (inclisiran) provided an effective lipid lowering activity (-50 %) after an initial subcutaneous dose, repeated after 3 months and followed by a maintenance dose every 6 months. These problems could be overcome by the development of small chemical molecules anti PCSK9 as oral therapy for controlling hypercholesterolemia. In the present review, we summarized the pharmacological properties of oral anti PCSK9 molecules that are currently under clinical development (DC371739, CVI-LM001, and AZD0780), including the mimetic peptides enlicitide decanoate (MK-0616) and NNC0385-0434."

Journal • Review • Cardiovascular • Dyslipidemia • Metabolic Disorders

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=48 | Recruiting | Sponsor: AstraZeneca | Not yet recruiting ➔ Recruiting

Enrollment open • Dyslipidemia • Metabolic Disorders

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 | Not yet recruiting | Sponsor: AstraZeneca

New P1 trial • Dyslipidemia • Metabolic Disorders