AZD0780, a novel oral PCSK9 inhibitor, demonstrated significant LDL cholesterol (LDL-C) reduction in PURSUIT Phase IIb trial
AstraZeneca's AZD0780, a novel once-daily oral PCSK9 inhibitor, demonstrated significant results in the PURSUIT Phase IIb trial. The drug achieved a 50.7% reduction in LDL-C when administered with standard-of-care statin therapy, compared to placebo over 12 weeks.
The trial showed that 84% of participants receiving AZD0780 30mg reached their recommended LDL-C target (<70 mg/dL), versus only 13% in the control group. The effectiveness was consistent across moderate and high-intensity statin doses. The drug was generally well-tolerated, with adverse events comparable between treatment (38.2%) and placebo (32.6%) groups, and similar discontinuation rates (1.5% vs 2.3%).
AZD0780 di AstraZeneca, un nuovo inibitore orale del PCSK9 da assumere una volta al giorno, ha mostrato risultati significativi nella fase IIb dello studio PURSUIT. Il farmaco ha raggiunto una riduzione del 50,7% del LDL-C quando somministrato insieme alla terapia standard con statine, rispetto al placebo nel corso di 12 settimane.
Lo studio ha rivelato che l'84% dei partecipanti che ricevevano AZD0780 30mg ha raggiunto il target raccomandato di LDL-C (<70 mg/dL), rispetto solo al 13% nel gruppo di controllo. L'efficacia è stata costante tra le dosi di statine a intensità moderata e alta. Il farmaco è stato generalmente ben tollerato, con eventi avversi comparabili tra i gruppi di trattamento (38,2%) e placebo (32,6%), e tassi di interruzione simili (1,5% contro 2,3%).
AZD0780 de AstraZeneca, un nuevo inhibidor oral de PCSK9 que se toma una vez al día, demostró resultados significativos en el ensayo de fase IIb PURSUIT. El fármaco logró una reducción del 50,7% en LDL-C cuando se administró junto con la terapia estándar de estatinas, en comparación con el placebo durante 12 semanas.
El ensayo mostró que el 84% de los participantes que recibieron AZD0780 30mg alcanzaron su objetivo recomendado de LDL-C (<70 mg/dL), frente al 13% en el grupo de control. La eficacia fue consistente en dosis de estatinas de intensidad moderada y alta. El fármaco fue generalmente bien tolerado, con eventos adversos comparables entre los grupos de tratamiento (38,2%) y placebo (32,6%), y tasas de interrupción similares (1,5% frente a 2,3%).
아스트라제네카의 AZD0780, 하루에 한 번 복용하는 새로운 경구용 PCSK9 억제제는 PURSUIT 2b 단계 시험에서 중요한 결과를 보여주었습니다. 이 약물은 표준 치료인 스타틴 요법과 함께 투여되었을 때 LDL-C를 50.7% 감소시켰으며, 이는 12주 동안 위약과 비교한 결과입니다.
시험 결과, AZD0780 30mg을 받은 참가자의 84%가 권장 LDL-C 목표(<70 mg/dL)를 달성한 반면, 대조군에서는 단 13%만이 달성했습니다. 효과는 중간 및 고강도 스타틴 복용량에서 일관되었습니다. 이 약물은 일반적으로 잘 견디는 편이며, 치료군(38.2%)과 위약군(32.6%) 간의 부작용은 비슷했으며, 중단율도 유사했습니다(1.5% 대 2.3%).
AZD0780 d'AstraZeneca, un nouvel inhibiteur oral de PCSK9 à prendre une fois par jour, a montré des résultats significatifs lors de l'essai de phase IIb PURSUIT. Le médicament a atteint une réduction de 50,7% du LDL-C lorsqu'il a été administré avec une thérapie standard de statines, par rapport au placebo sur 12 semaines.
L'essai a montré que 84% des participants recevant AZD0780 30mg ont atteint leur objectif recommandé de LDL-C (<70 mg/dL), contre seulement 13% dans le groupe témoin. L'efficacité était cohérente entre les doses de statines à intensité modérée et élevée. Le médicament a généralement été bien toléré, avec des événements indésirables comparables entre les groupes de traitement (38,2%) et de placebo (32,6%), et des taux d'abandon similaires (1,5% contre 2,3%).
AZD0780 von AstraZeneca, ein neuartiger einmal täglich einzunehmender PCSK9-Inhibitor, zeigte signifikante Ergebnisse in der PURSUIT Phase IIb-Studie. Das Medikament erreichte eine Reduktion von 50,7% des LDL-C, als es zusammen mit der Standardtherapie mit Statinen verabreicht wurde, im Vergleich zu Placebo über 12 Wochen.
Die Studie zeigte, dass 84% der Teilnehmer, die AZD0780 30mg erhielten, ihr empfohlenes Ziel für LDL-C (<70 mg/dL) erreichten, während es im Kontrollgruppe nur 13% waren. Die Wirksamkeit war bei moderaten und hohen Statindosen konsistent. Das Medikament wurde im Allgemeinen gut vertragen, mit vergleichbaren unerwünschten Ereignissen zwischen der Behandlungsgruppe (38,2%) und der Placebogruppe (32,6%) sowie ähnlichen Abbruchraten (1,5% vs. 2,3%).
- Significant 50.7% reduction in LDL-C levels
- 84% of patients reached target LDL-C levels vs 13% in control group
- Consistent efficacy across different statin intensity doses
- Favorable safety profile with low discontinuation rates
- Novel oral administration without fasting restrictions
- Still in Phase IIb trials, requiring further studies before potential approval
- Slightly higher adverse events rate (38.2%) compared to placebo (32.6%)
Insights
AstraZeneca's Phase IIb PURSUIT trial results for AZD0780 represent a significant advancement in cardiovascular disease management. The oral PCSK9 inhibitor achieved a
What's particularly compelling is that
The oral administration route without fasting restrictions addresses a critical unmet need in this therapeutic area. Current injectable PCSK9 inhibitors face adherence challenges, with many eligible patients declining treatment due to injection requirements. This convenient once-daily oral option could substantially expand the addressable market beyond what existing injectables have captured.
Safety data appears reassuring with adverse event rates comparable to placebo. This favorable tolerability profile, if maintained in larger studies, would support broad adoption if approved.
While promising, these are still mid-stage results. The path to approval requires successful completion of larger Phase III trials, likely including cardiovascular outcomes data. AstraZeneca hasn't disclosed timeline details, but AZD0780 represents a potential competitive advantage in their cardiovascular portfolio that addresses the estimated
AstraZeneca's AZD0780 data delivers precisely what investors want to see in mid-stage clinical results. The
This positions AstraZeneca to potentially disrupt the PCSK9 inhibitor market, currently dominated by injectable options from Amgen (Repatha) and Regeneron/Sanofi (Praluent). Despite proven efficacy, these injectables have faced commercial challenges due to administration barriers and initial reimbursement hurdles. An effective oral alternative could capture significant market share and potentially expand the overall treatment population.
The cardiovascular disease market represents substantial commercial opportunity. High cholesterol affects approximately 40% of adults globally, with only a fraction achieving adequate control on statins alone. The
For AstraZeneca's broader portfolio strategy, AZD0780 complements their established cardiovascular franchise and aligns with their focus on chronic diseases requiring long-term therapy. This fits their strategic emphasis on developing differentiated assets in core therapeutic areas.
While commercial impact remains years away pending completion of pivotal trials and regulatory review, these results justify continued investment in the program. They also provide additional pipeline validation for AstraZeneca's cardiovascular research capabilities beyond their established products like Brilinta and Farxiga.
New late-breaking clinical trial data presented at ACC and published simultaneously in JACC show benefit of investigational medicine AZD0780 on top of standard of care
These new data were presented today at the American College of Cardiology’s (ACC) Annual Scientific Session & Expo in
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
High LDL-C (≥70 mg/dL), a common type of dyslipidemia, is a key risk factor for atherosclerotic cardiovascular disease, including stroke and heart attack, and a significant public health concern.3 It is estimated that more than
Dr. Michael J Koren, MD, CEO & Medical Director of Jacksonville Center for Clinical Research,
Sharon Barr, Executive Vice President, BioPharmaceuticals R&D, AstraZeneca, said: “These new data reflect AZD0780’s ability to reduce LDL cholesterol in patients who need more options to manage their cholesterol and related risks when standard-of-care therapy is not enough. As a novel small molecule oral PCSK9 inhibitor that can be taken without fasting restrictions, AZD0780 has the potential to be a game changer that could offer LDL-C lowering with greater convenience for patients. Our work in dyslipidemia builds on our strong heritage in cardiovascular, renal and metabolic diseases where we are advancing novel therapies, alone or in combination with other molecules in our extensive portfolio, that could redefine treatment standards and patient outcomes.”
AZD0780 was generally well tolerated, and adverse events (AEs) were comparable between the total AZD0780 treatment groups (
Data from PURSUIT are consistent with Phase I findings presented at European Atherosclerosis Society (EAS) 2024.8
Notes
About Dyslipidemia
Elevated LDL-C levels in plasma is a key risk factor for cardiovascular disease and is estimated to cause 4.4 million deaths worldwide annually.3 Despite current treatment options, the global burden of dyslipidemia is on the rise.4 More than
PURSUIT
PURSUIT is a Phase IIb, multicenter, randomized, parallel-group, double-blind, placebo-controlled, dose-ranging study to evaluate the efficacy, safety and tolerability of AZD0780 in participants with dyslipidemia.2
PURSUIT assessed the efficacy, safety and tolerability of different doses of AZD0780 on LDL-C levels in patients with hypercholesterolemia. 428 patients on stable standard-of-care therapy with moderate- or high-intensity statins with or without ezetimibe with LDL-C levels ≥70 and <190 mg/dL were randomized (1:1:1:1:1) to receive AZD0780 (1 mg, 3 mg, 10 mg and 30 mg daily) or matching placebo. 426 patients started treatment.2
The primary objective of the study was to measure the effect of different doses of AZD0780 given once daily on LDL-C levels in patients with dyslipidemia receiving standard-of-care statins. The effect of AZD0780 versus placebo on other lipid parameters and inflammatory markers was also investigated. The concentration of AZD0780 in blood at specific timepoints was measured, and the safety and tolerability of AZD0780 evaluated.2
AZD0780
AZD0780 is an oral, small molecule PCSK9 inhibitor that is being developed by AstraZeneca as an innovative therapy for patients with elevated low-density lipoprotein cholesterol (LDL-C) levels which cannot be controlled by statins alone.2 PCSK9 is a well-known and validated target in LDL-C metabolism and inhibiting PCSK9 signalling has shown to be effective in reducing LDL-C levels in plasma.2 Lower LDL-C levels are associated with a reduction in the risk of long-term cardiovascular disease and major cardiovascular events.9 AstraZeneca is investigating the potential of AZD0780 as an oral small-molecule for use as a monotherapy or in fixed-dose combinations with other therapies in our extensive portfolio. Data from PURSUIT are consistent with Phase I findings for AZD0780 which demonstrated a statistically significant reduction of
AstraZeneca in CVRM
Cardiovascular, Renal and Metabolism (CVRM), part of BioPharmaceuticals, forms one of AstraZeneca’s main disease areas and is a key growth driver for the Company. By following the science to understand more clearly the underlying links between the heart, kidneys, liver and pancreas, AstraZeneca is investing in a portfolio of medicines for organ protection by slowing or stopping disease progression, and ultimately paving the way towards regenerative therapies. The Company’s ambition is to improve and save the lives of millions of people, by better understanding the interconnections between CVRM diseases and targeting the mechanisms that drive them, so we can detect, diagnose and treat people earlier and more effectively.
AstraZeneca
AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialization of prescription medicines in Oncology, Rare Diseases and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in
References
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Koren M, et al. Efficacy and safety of AZD0780, an oral small molecule PCSK9 inhibitor for treatment of hypercholesterolemia: Results from a Ph2b randomized placebo-controlled clinical trial. Presented at: American College of Cardiology Annual Scientific Session (ACC 2025); 2025 Mar 29-31;
Chicago, IL. - Koren MJ, et al. An oral, small molecule PCSK9 inhibitor for treatment of hypercholesterolemia: the PURSUIT randomized trial. J Am Coll Cardiol. 2025.
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World Heart Federation. Cholesterol. Available at: https://world-heart-federation.org/what-we-do/cholesterol/#:~:text=High%20blood%20cholesterol%20is%20one,or%
207.8% 25% 20of%20all%20deaths [Last accessed: March 2025]. - Pirillo A, et al. Global epidemiology of dyslipidaemias. Nat Rev Cardiol. 2021;18(10):689-700.
- Cannon CP, et al. Use of lipid-lowering therapies over 2 years in GOULD, a registry of patients with atherosclerotic cardiovascular disease in the US. JAMA Cardiol. 2021;6:1060-1068.
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Ray KK, et al. Treatment gaps in the implementation of LDL cholesterol control among high- and very high-risk patients in
Europe between 2020 and 2021: the multinational observational SANTORINI study. Lancet Reg Health Eur. 2023;29:100624. -
Underberg J, et al. LDL-C target attainment in secondary prevention of ASCVD in
the United States : barriers, consequences of nonachievement, and strategies to reach goals. Postgrad Med. 2022;134:752-762. - Vega R, et al. AZD0780, the first oral small molecule PCSK9 inhibitor for the treatment of hypercholesterolemia: results from a randomized, single-blind, placebo-controlled phase 1 trial. Atherosclerosis. 2024;395:118514.
- Domanski MJ, et al. Time course of LDL cholesterol exposure and cardiovascular disease event risk. J Am Coll Cardiol. 2020;76(13):1507-1516.
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FAQ
What were the key results of AstraZeneca's AZD0780 PURSUIT Phase IIb trial?
How is AZD0780 different from existing PCSK9 inhibitors?
What were the safety results for AZD0780 in the PURSUIT trial?
How many patients currently don't reach their LDL-C targets with existing treatments?
