AZD0780 / AstraZeneca - LARVOL DELTA

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

AZD0780, the first oral small molecule inhibitor of PCSK9: Results from a randomized, single-blind, placebo controlled Phase 1 trial (CVCT USA 2024) - No abstract available

Clinical • P1 data

AZD0780-ABPM: A Study to Assess the Effect of AZD0780 on Ambulatory Blood Pressure (clinicaltrials.gov) - P2 | N=172 | Recruiting | Sponsor: AstraZeneca

New P2 trial • Atherosclerosis • Cardiovascular • Dyslipidemia

A Study to Investigate the Pharmacokinetics of AZD0780 When Administered Alone and in Combination With Itraconazole and Carbamazepine in Healthy Participants Aged 18 to 75 Years of Age (clinicaltrials.gov) - P1 | N=42 | Recruiting | Sponsor: AstraZeneca

Combination therapy • New P1 trial • Dyslipidemia

PURSUIT: A Study to Assess the Efficacy, Safety and Tolerability of Different Doses of AZD0780 in Patients With Dyslipidemia (clinicaltrials.gov) - P2 | N=428 | Completed | Sponsor: AstraZeneca | Active, not recruiting ➔ Completed

Trial completion • Dyslipidemia • Metabolic Disorders

A Phase I Study to Investigate the Effect of Renal Impairment on the Pharmacokinetics, Safety, and Tolerability of AZD0780 (clinicaltrials.gov) - P1 | N=42 | Recruiting | Sponsor: AstraZeneca

New P1 trial • Renal Disease

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

New P1 trial • Hepatology

AZD0780 - an oral PCSK9 inhibitor with a novel mode of action for the treatment of cardiovascular disease (ACS-Fall 2024) - "This led to the development of a new class of small molecule PCSK9 inhibitors that includes our clinical candidate AZD0780. Unlike the peptidic or mAb-based PCSK9 inhibitors, AZD0780 does not inhibit the PCSK9-LDLR PPI but instead inhibits PCSK9 via a novel mode of action.In a Phase I clinical study, AZD0780 was generally safe and well-tolerated and has recently progressed to Phase 2 clinical studies.We will describe the hit finding and lead optimisation program, the preclinical profile of AZD0780 and details of its mode of action as well as a summary of the Phase I clinical trial results."

Cardiovascular

A Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AZD0780 in Healthy Subjects (clinicaltrials.gov) - P1 | N=183 | Completed | Sponsor: AstraZeneca | Active, not recruiting ➔ Completed

Trial completion • Dyslipidemia • Metabolic Disorders

PURSUIT: A Study to Assess the Efficacy, Safety and Tolerability of Different Doses of AZD0780 in Patients With Dyslipidemia (clinicaltrials.gov) - P2 | N=428 | Active, not recruiting | Sponsor: AstraZeneca | Recruiting ➔ Active, not recruiting

Enrollment closed • Dyslipidemia • Metabolic Disorders

A Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AZD0780 in Healthy Subjects (clinicaltrials.gov) - P1 | N=184 | Active, not recruiting | Sponsor: AstraZeneca | Recruiting ➔ Active, not recruiting

Enrollment closed • Dyslipidemia • Metabolic Disorders

PURSUIT: A Study to Investigate the Effect of Different Doses of AZD0780 on Low-Density Lipoprotein Cholesterol (LDL-C) Levels Compared With Placebo and Its Safety and Tolerability in Participants 18 to 75 Years of Age With Dyslipidemia (clinicaltrials.gov) - P2 | N=375 | Recruiting | Sponsor: AstraZeneca | Not yet recruiting ➔ Recruiting | N=175 ➔ 375

Enrollment change • Enrollment open • Dyslipidemia • Metabolic Disorders