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阿斯利康公布baxdrostat在Bax24 III期试验的阳性结果

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  • Baxdrostat demonstrated a statistically significant placebo-adjusted reduction of 13.9 mmHg in night-time ambulatory systolic blood pressure at 12 weeks with a safety profile consistent with the BaxHTN trial

  • Full results presented at the American Heart Association Scientific Sessions 2025


9 November 2025--Positive full results from the Bax24 Phase III trial showed baxdrostat demonstrated a statistically significant and highly clinically meaningful reduction in ambulatory 24-hour average systolic blood pressure (SBP) compared with placebo at 12 weeks. Patients with treatment-resistant hypertension (rHTN) received baxdrostat 2mg or placebo on top of standard of care.1 Efficacy was observed throughout the 24-hour period, including early morning, when patients with hypertension are at a higher risk of cardiovascular events.2-4

 

Baxdrostat met the primary endpoint in the Bax24 Phase III trial, delivering clinically meaningful and consistent blood pressure reductions in patients with treatment-resistant hypertension. At 12 weeks, the placebo-adjusted reduction in ambulatory 24-hour average SBP was 14.0 mmHg (95% confidence interval [CI] -17.2, -10.8; p<0.0001).1 Baxdrostat was generally well tolerated, with a safety profile consistent with the BaxHTN trial.1,5

 

Baxdrostat demonstrated statistically significant and clinically meaningful reductions in key secondary endpoints, including ambulatory night-time average SBP (13.9 mmHg placebo-adjusted [95% CI -17.5, -10.3; p<0.0001]) and seated SBP (10.3 mmHg placebo-adjusted [95% CI -14.9, -5.6; p<0.0001]) consistent with data from the BaxHTN trial.1,5 Significantly more patients treated with baxdrostat (71%) achieved ambulatory 24-hour average SBP of less than 130 mmHg compared with patients receiving placebo (17%) (Odds ratio 15.2 [95% CI 6.6, 35.2; p<0.0001]).1

 

Dr. Bryan Williams, Chair of Medicine at University College London, primary investigator, said: “The landmark results from Bax24 Phase III trial demonstrate that patients with the hardest-to-control hypertension treated with baxdrostat achieved a highly clinically meaningful 14 mmHg placebo-adjusted reduction in 24-hour systolic blood pressure, which could transform treatment practice. It's remarkable to see this magnitude of reduction coupled with the fact that just over 70% of baxdrostat patients achieved guideline targets, consistently over 24 hours.”

 

Sharon Barr, Executive Vice President, BioPharmaceuticals R&D, said: “The Bax24 data demonstrate the significant impact that baxdrostat’s long half-life and highly selective inhibition of aldosterone synthase can have in improving 24-hour and overnight blood pressure for patients with resistant hypertension. Patients with elevated night-time blood pressure are especially vulnerable to cardiovascular events, including heart attack and stroke. Together with the results from BaxHTN, these findings demonstrate the potential of baxdrostat to redefine what is possible for the millions of patients whose hypertension remains uncontrolled despite current therapies.”

 

There are 1.4 billion people worldwide living with hypertension.6 In the US, approximately 50% of patients living with hypertension on multiple treatments do not have their blood pressure under control.7 Consistent 24-hour blood pressure control is an important clinical outcome in patients with hard-to-control hypertension.8-10 Multiple studies have demonstrated that 24-hour blood pressure is a more powerful predictor of cardiovascular events than a clinic-based measurement.4,11 When 24-hour average systolic blood pressure rises by 9.5 mmHg, the risk of all-cause mortality increases by 30%.4

 

Full results from the Bax24 trial were presented today at the Emerging Opportunities for Managing Cardiometabolic Syndrome late breaker session at the American Heart Association (AHA) Scientific Sessions 2025. These data will be shared with regulatory authorities around the world.

 

Baxdrostat is designed to lower blood pressure by specifically inhibiting aldosterone, a key hormone that raises blood pressure and increases the risk of heart and kidney problems. Phase I studies show baxdrostat reached peak levels in the blood within 2 to 4 hours and had a half-life of about 26 to 30 hours.12,13 Baxdrostat is currently being investigated as a monotherapy for hypertension13-16 and primary aldosteronism,17 and in combination with dapagliflozin for chronic kidney disease18,19 and the prevention of heart failure in high-risk patients.20

 

Hard-to-control hypertension


Hypertension is a medical condition characterised by consistently high blood pressure levels, affecting an estimated 1.4 billion people worldwide.6,21,22 Over time, this can damage blood vessels and vital organs, increasing the risk of serious health problems such as heart attack, stroke, heart failure and kidney disease.20,21 An observational study of nearly 60,000 patients studied over a median of 9.7 years showed that a 9.5 mmHg increase in 24-hour ambulatory SBP was associated with a 30% increase in risk of all-cause mortality and 41% increase in risk of cardiovascular death.4 Studies have shown that increased night-time blood pressure is associated with higher cardiovascular risk,8,11 and patients with hypertension have a higher risk of cardiovascular events like heart attack, stroke and death around the time of their morning blood pressure surge.2,3

 

Hard-to-control (uncontrolled and resistant) hypertension remains a major public health challenge.23 Despite lifestyle changes and the use of multiple medications, approximately 50% of patients in the US who are being treated for hypertension still do not have their blood pressure under control.7 Uncontrolled hypertension refers to persistently elevated blood pressure despite the use of two or more medications, while resistant hypertension, a more severe form, remains elevated despite treatment with three or more medications.7,21 Guidelines currently recommend that in patients with hypertension, treated BP values should be targeted to 130/80 mmHg or lower in most patients.21,22

 

A key contributor to hard-to-control hypertension is aldosterone, a hormone that raises blood pressure by promoting sodium and water retention.24,25 Elevated aldosterone levels, along with factors such as obesity, high salt intake, and various genetic or secondary conditions,26 are strongly associated with poor blood pressure control. When left untreated, hypertension significantly increases the risk of cardiovascular and kidney-related complications.21,22

 

Bax24 trial


The Phase III Bax24 trial16 is a randomised, double-blind, placebo-controlled, parallel group study to evaluate the effects of 2mg baxdrostat versus placebo, administered once a day (QD) orally, on the reduction of ambulatory SBP, as well as safety and tolerability in participants with resistant hypertension. A total of 218 patients were randomised in a 1:1 ratio to receive baxdrostat 2mg or placebo once daily during a 12-week double blind period. The primary efficacy endpoint was the change from baseline in ambulatory 24-hour average SBP at Week 12.

 

Additional secondary endpoints include the effect of baxdrostat versus placebo on change from baseline in ambulatory night-time average SBP, change from baseline in ambulatory daytime average SBP, change from baseline in seated SBP, the number of participants achieving ambulatory 24-hour average SBP of less than 130 mmHg , change from baseline in ambulatory 24-hour average diastolic blood pressure (DBP), change from baseline in ambulatory night-time average DBP, change from baseline in the average ambulatory daytime average DBP, change from baseline on seated DBP and the number of participants achieving a nocturnal SBP dipping of greater than or equal to 10%, all measured at Week 12. Occurrence of adverse events was evaluated during the 12-week treatment period as well as during a 2-week safety follow-up period.

​

Baxdrostat


Baxdrostat is a potential first-in-class, highly selective and potent, oral, small molecule that inhibits aldosterone synthase,12 an enzyme encoded by the CYP11B2 gene, which is responsible for the synthesis of aldosterone in the adrenal gland.24 In clinical trials, baxdrostat was observed to significantly lower aldosterone levels without affecting cortisol levels across a wide range of doses.13,27 Baxdrostat is currently being investigated in clinical trials as a monotherapy for hypertension13-16 and primary aldosteronism,17 and in combination with dapagliflozin for chronic kidney disease and hypertension,18,19 and the prevention of heart failure in high-risk patients.20

 

AstraZeneca acquired baxdrostat through its purchase of CinCor Pharma, Inc. in February 2023.28

 

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 (LSE/STO/Nasdaq: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialisation of prescription medicines in Oncology, Rare Diseases, and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca’s innovative medicines are sold in more than 125 countries and used by millions of patients worldwide. 

 

References

  1. Williams B, et al. Effect of baxdrostat on 24-hour ambulatory blood pressure in patients with resistant hypertension: the Bax24 trial. Presented at: American Heart Association Scientific Sessions 2025; November 7–10, 2025; New Orleans, LA.

  2. Renna NF, et al. Morning blood pressure surge as a predictor of cardiovascular events in patients with hypertension. Blood Press Monit. 2023;28(3):149-157 

  3. Kario K et al. Morning hypertension: the strongest independent risk factor for stroke in elderly hypertensive patients. Hypertens Res. 2006;29(8):581-7. 

  4. Staplin N, et al. Relationship between clinic and ambulatory blood pressure and mortality: an observational cohort study in 59 124 patients. Lancet. 2023;401(10393):2041-2050.  

  5. Flack JM, et al. Efficacy and Safety of Baxdrostat in Uncontrolled and Resistant Hypertension. N Engl J Med. 2025. Aug 30:10.1056/NEJMoa2507109. doi: 10.1056/NEJMoa2507109. 

  6. World Health Organization. Global report on hypertension 2025: high stakes: turning evidence into action. 2025.  https://iris.who.int/handle/10665/382841. Accessed September 2025. 

  7. Carey RM, et al. Prevalence of Apparent Treatment-Resistant Hypertension in the United States. Hypertension. 2019;73(2):424-431.

  8. Narita K, et al. Nighttime Home Blood Pressure Is Associated With the Cardiovascular Disease Events Risk in Treatment-Resistant Hypertension. Hypertension. 2022;79(2):e18-e20 

  9. Kario K, et al. Nighttime Blood Pressure Phenotype and Cardiovascular Prognosis. Circulation. 2020;142(19):1810-1820 

  10. Williams B, et al. 2018 ESC/ESH Guidelines for the management of arterial hypertension: The Task Force for the management of arterial hypertension of the European Society of Cardiology (ESC) and the European Society of Hypertension (ESH). European Heart Journal. 2018;39(33):3021-3104. 

  11. Niiranen TJ, Mäki J, Puukka P, Karanko H, Jula AM. Office, home, and ambulatory blood pressures as predictors of cardiovascular risk. Hypertension. 2014 Aug;64(2):281-6. 

  12. Bogman K, et al. Preclinical and early clinical profile of a highly selective and potent oral inhibitor of aldosterone synthase (CYP11B2). Hypertension. 2017;69(1):189-196.

  13. Freeman MW, et al. Results from a phase 1, randomized, double-blind, multiple ascending dose study characterizing the pharmacokinetics and demonstrating the safety and selectivity of the aldosterone synthase inhibitor baxdrostat in healthy volunteers. Hypertens Res. 2023;46(1):108-118.

  14. ClinicalTrials.gov.A Study to Investigate the Efficacy and Safety of Baxdrostat in Participants With Uncontrolled Hypertension on Two or More Medications Including Participants With Resistant Hypertension (BaxHTN). Available at: https://clinicaltrials.gov/study/NCT06034743. Accessed October 2025. 

  15. ClinicalTrials.gov. A Study to Investigate the Efficacy and Safety of Baxdrostat in Participants With Uncontrolled Hypertension on Two or More Medications Including Participants With Resistant Hypertension (BaxAsia). Available at: https://clinicaltrials.gov/study/NCT06344104. Accessed October 2025. 

  16. ClinicalTrials.gov. A Study to Investigate the Effect of Baxdrostat on Ambulatory Blood Pressure in Participants With Resistant Hypertension (Bax24). Available at:  https://clinicaltrials.gov/study/NCT06168409. Accessed October 2025. 

  17. ClinicalTrials.gov. A Study to Assess Efficacy and Safety of Baxdrostat in Participants With Primary Aldosteronism (BaxPA). Available at: https://clinicaltrials.gov/study/NCT07007793. Accessed October 2025. 

  18. ClinicalTrials.gov. A Phase III Study to Investigate the Efficacy and Safety of Baxdrostat in Combination With Dapagliflozin on CKD Progression in Participants With CKD and High Blood Pressure. Available at: https://clinicaltrials.gov/study/NCT06268873. Accessed October 2025. 

  19. ClinicalTrials.gov. A Phase III Renal Outcomes and Cardiovascular Mortality Study to Investigate the Efficacy and Safety of Baxdrostat in Combination With Dapagliflozin in Participants With Chronic Kidney Disease and High Blood Pressure (BaxDuo-Pacific). Available at: https://clinicaltrials.gov/study/NCT06742723. Accessed October 2025.

  20. ClinicalTrials.gov. Phase III Study Investigating Heart Failure and Cardiovascular Death With Baxdrostat in Combination With Dapagliflozin (Prevent-HF). Available at:  https://clinicaltrials.gov/study/NCT06677060. Accessed October 2025. 

  21. McEvoy JW, et al. 2024 ESC Guidelines for the management of elevated blood pressure and hypertension. Eur Heart J. 2024;45(38):3912-4018.

  22. Jones DW, et al. 2025 AHA/ACC/AANP/AAPA/ABC/ACCP/ACPM/AGS/AMA/ASPC/NMA/PCNA/SGIM Guideline for the Prevention, Detection, Evaluation and Management of High Blood Pressure in Adults: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation 2025;152:e114–e218.

  23. NCD Risk Factor Collaboration (NCD-RisC). Worldwide trends in hypertension prevalence and progress in treatment and control from 1990 to 2019: a pooled analysis of 1201 population-representative studies with 104 million participants. Lancet. 2021;398(10304):957-980.

  24. Cannavo A, et al. Aldosterone and mineralocorticoid receptor system in cardiovascular physiology and pathophysiology. Oxid Med Cell Longev. 2018;2018:1204598.

  25. Inoue K, et al. Serum aldosterone concentration, blood pressure, and coronary artery calcium: The multi-ethnic study of atherosclerosis. Hypertension. 2020;76(1):113-120.

  26. van Oort S, et al. Association of cardiovascular risk factors and lifestyle behaviors with hypertension: a mendelian randomization study. Hypertension. 2020;76(6):1971-1979. 

  27. Freeman MW, et al. Phase 2 trial of baxdrostat for treatment-resistant hypertension. N Engl J Med. 2023;388(5):395-405.

  28. AstraZeneca 2023. Acquisition of CinCor Pharma complete. https://www.astrazeneca.com/media-centre/press-releases/2023/astrazeneca-acquires-cincor-for-cardiorenal-asset.html. Accessed October 2025.  

文章关键词： 阿斯利康baxdrostatBax24 III期试验
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