laroprovstat (AZD0780) / AstraZeneca - LARVOL DELTA

Pharmacological management of elevated LDL in patients with hypercholesterolaemia and mixed dyslipidaemia. (PubMed, Expert Opin Pharmacother) - "Ezetimibe is the next recommended therapy to add, and bempedoic acid provides another oral drug that can be added or substituted for the statins. The injectable proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are the most effective drugs in reducing LDL-C, but their uptake has not met expectations because of issues of cost and patients' reluctance to take injection therapy. The oral PCSK9 inhibitors in development and obicetrapib appear safe and very effective and if approved they should provide useful alternatives for reaching LDL-C goals but the problem of long-term adherence to therapy will remain."

Journal • Review • Atherosclerosis • Cardiovascular • Dyslipidemia • Metabolic Disorders • Mixed Hyperlipidemia

A Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of AZD0780 in Participants With Dyslipidaemia (clinicaltrials.gov) - P2/3 | N=360 | Recruiting | Sponsor: AstraZeneca | Trial completion date: Jun 2027 ➔ Feb 2027 | Trial primary completion date: Jun 2027 ➔ Feb 2027

Trial completion date • Trial primary completion date • Dyslipidemia

D7960C00015: A Trial to Test How AZD0780 Affects Serious Heart, Stroke, or Vascular Problems in Patients with Heart, Stroke or Vascular Disease or at High Risk for Such Issues (clinicaltrialsregister.eu) - P2/3 | N=3531 | Recruiting | Sponsor: AstraZeneca AB

Adverse events • New P2/3 trial • Atherosclerosis • Cardiovascular

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

Enrollment open

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 | Not yet recruiting | Sponsor: AstraZeneca

New P1 trial

Pharmacokinetics, Disposition, and Biotransformation of Laroprovstat in Humans: In Vivo and In Vitro Evaluations. (PubMed, J Clin Pharmacol) - "Laroprovstat was incubated in human hepatic spheroids from two different donors with and without ketoconazole to examine metabolite formation. Laroprovstat was well tolerated with no new safety concerns. These studies successfully characterized the ADME properties of laroprovstat."

Journal • PK/PD data • Preclinical • Dyslipidemia • Metabolic Disorders

Safety and efficacy of oral PCSK9 inhibitors in hypercholesterolemia: A systematic review and network meta-analysis. (PubMed, Endocr Pract) - "Limited short-term data suggest that oral PCSK9i are reasonably safe and effective, reducing LDL-C and improving other lipids. Longer, larger RCTs are required to confirm safety, efficacy, and cardiovascular benefits before broader use."

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

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

Enrollment open • 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=3046 | Active, not recruiting | Sponsor: AstraZeneca | Recruiting ➔ Active, not recruiting

Enrollment closed • 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=455 | Active, not recruiting | Sponsor: AstraZeneca | Recruiting ➔ Active, not recruiting

Enrollment closed • Dyslipidemia • Familial Hypercholesterolemia • Heterozygous Familial Hypercholesterolemia

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 | Completed | Sponsor: AstraZeneca | Active, not recruiting ➔ Completed

Trial completion

A Phase I, Open-label, Crossover 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 | Not yet recruiting | Sponsor: AstraZeneca

New P1 trial

CADD-engineered peptide protacs efficiently target PCSK9 for hypercholesterolemia in vivo. (PubMed, Metabolism) - "Cadd4 represents a promising CADD-designed therapeutic strategy for cholesterol management by targeting intracellular PCSK9 for degradation. This approach overcomes key limitations of existing therapies and underscores the potential of targeted protein degradation in cardiovascular disease treatment."

Journal • Preclinical • Cardiovascular • Dyslipidemia • Metabolic Disorders • Targeted Protein Degradation • LDLR

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 | Active, not recruiting | Sponsor: AstraZeneca | Recruiting ➔ Active, not recruiting

Enrollment closed

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