Author: admin

*The main analyses of ambulatory BP endpoints include patients with valid ambulatory blood pressure monitoring at both baseline and Week 12, without imputation of missing data.

LS, least squares; n Number of subjects in analysis; N Number of subjects per treatment group

Notes

Hard-to-control hypertension
Hypertension is a medical condition characterized 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 randomized, 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 randomized 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 hypertension^13-16 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 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 Cambridge, UK, AstraZeneca’s innovative medicines are sold in more than 125 countries and used by millions of patients worldwide. Please visit www.astrazeneca-us.com and follow the Company on social media @AstraZeneca.

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Lauren-Jei McCarthy                                                              +1 347 918 7001

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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.