Baxdrostat demonstrated statistically significant and clinically meaningful reduction in systolic blood pressure in patients with hard-to-control hypertension in the BaxHTN Phase III ​trial

Baxdrostat 2mg lowered systolic blood pressure by 15.7 mmHg (9.8 mmHg placebo-adjusted) from baseline, and was generally well tolerated with no unanticipated safety findings

Full results presented at the European Society of Cardiology Congress 2025 and published in the New England Journal of Medicine

Positive full results from the ​BaxHTN Phase III trial showed ​baxdrostat demonstrated a statistically significant and clinically meaningful reduction in mean seated systolic blood pressure (SBP) at two doses (2mg and 1mg) compared with placebo at 12 weeks. Results were seen in patients with hard-to-control (uncontrolled and resistant) hypertension who received baxdrostat or placebo on top of standard of care.

These data were presented today in a Hot Line session at the European Society of Cardiology (ESC) Congress 2025 and also simultaneously published in the New England Journal of Medicine.

Baxdrostat met the primary and all secondary endpoints in the BaxHTN Phase III trial, delivering meaningful and sustained blood pressure reductions in patients with hard-to-control hypertension. At week 12, the absolute reduction from baseline in mean seated SBP was 15.7 mmHg (95% confidence interval [CI], -17.6 to -13.7) and placebo-adjusted reduction was 9.8 mmHg (95% CI, -12.6 to -7.0; p<0.001) for the 2mg dose. For the 1mg dose, the absolute reduction from baseline was 14.5 mmHg (95% CI, -16.5 to -12.5) and placebo-adjusted reduction was 8.7 mmHg (95% CI, -11.5 to -5.8; p<0.001). The reduction in mean seated SBP with placebo was 5.8 mmHg (95% CI, -7.9 to -3.8). Results were consistent across both uncontrolled and treatment-resistant subgroups.

Baxdrostat was generally well tolerated with no unanticipated safety findings, and low rates of confirmed hyperkalemia (>6 mmol/L in both dose groups [1.1% each]) compared with placebo (0.0%). The safety profile of baxdrostat was consistent with its mechanism of action, and most adverse events were mild.

The trial also met all confirmatory secondary endpoints with baxdrostat. This included demonstration of durable long-term blood pressure reduction with baxdrostat 2mg. Both 2mg and 1mg doses also led to greater reductions in diastolic blood pressure and nearly tripled the odds of patients reaching their target SBP <130 mmHg compared with placebo.

In a prespecified exploratory analysis of a subgroup of patients, baxdrostat meaningfully reduced 24-hour and ambulatory nighttime SBP compared with placebo, key indicators of sustained blood pressure control and reduced cardiovascular risk. The 2mg dose lowered 24-hour SBP by 16.9 mmHg (95% CI, -25.6 to -8.3), and the pooled 2mg and 1mg doses lowered nighttime SBP by 11.7 mmHg (95% CI, -19.5 to -3.8). The Bax24 Phase III trial, evaluating 24-hour ambulatory effects, is expected to read out later this year.

Dr. Bryan Williams, Chair of Medicine at University College London, primary investigator, said: "Achieving a nearly 10 mmHg placebo-adjusted reduction in systolic blood pressure with baxdrostat in the BaxHTN Phase III trial is exciting, as this level of reduction is linked to substantially lower risk of heart attack, stroke, heart failure and kidney disease. These data show that aldosterone plays a greater role in hard-to-control hypertension than previously recognized, underscoring the importance of baxdrostat's novel mechanism of action, and potential impact for the millions of people living with hard-to-control hypertension despite being on multiple treatments."

Sharon Barr, Executive Vice President, BioPharmaceuticals R&D, said: "The BaxHTN Phase III results demonstrate baxdrostat's potential in tackling one of the toughest challenges in cardiovascular care, which is hypertension that is hard to control despite multiple therapies. We look forward to advancing our regulatory filings for baxdrostat with health authorities in the months ahead, in addition to rapidly progressing a robust clinical development program across indications where aldosterone plays a key role, including chronic kidney disease and heart failure prevention."

There are 1.3 billion people worldwide living with hypertension.¹ In the US, approximately 50% of patients living with hypertension on multiple treatments do not have their blood pressure under control.² Aldosterone dysregulation is increasingly recognized as one of the key biological drivers of the disease, contributing to elevated cardiovascular and renal risk.^3,4 A large meta-analysis found that lowering systolic blood pressure by 10 mmHg can reduce the risk of major adverse cardiovascular events by around 20%,⁵ underscoring the urgent need for new treatments that target hypertension at its source.

Baxdrostat is a potential first-in-class, highly selective aldosterone synthase inhibitor (ASI) that targets one of the hormones driving elevated blood pressure and increased cardiovascular and renal risk. It is currently being investigated in clinical trials enrolling more than 20,000 patients globally, as a monotherapy for hypertension and primary aldosteronism, and in combination with dapagliflozin for chronic kidney disease and hypertension, and the prevention of heart failure in patients with hypertension.

Notes

Hard-to-control hypertension

Hypertension is a medical condition characterized by consistently high blood pressure levels, affecting an estimated 1.3 billion people worldwide.^1,6,7 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.^6,7

Hard-to-control (uncontrolled and resistant) hypertension remains a major public health challenge.¹ 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.^1,2 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.^2,6

A key contributor to hard-to-control hypertension is aldosterone, a hormone that raises blood pressure by promoting sodium and water retention.^3,4 Elevated aldosterone levels, along with factors such as obesity, high salt intake, and various genetic or secondary conditions,⁸ are strongly associated with poor blood pressure control. When left untreated, hypertension significantly increases the risk of cardiovascular and kidney-related complications.^6,7

BaxHTN trial

The BaxHTN Phase III trial⁹ had three components to it that support the following endpoints: The primary endpoint was assessed during a 12-week double-blind, placebo-controlled period. A total of 796 patients were characterized in a 1:1:1 ratio to receive baxdrostat 2mg, 1mg or placebo once daily. The primary efficacy endpoint was the difference in mean change from baseline in seated SBP at week 12 between participants treated with baxdrostat (2mg or 1mg separately) and participants treated with placebo. Persistence of efficacy was assessed during a randomized withdrawal period from week 24 to week 32. Approximately 300 patients treated with baxdrostat 2mg were re-randomized in a 2:1 ratio to either continue receiving baxdrostat 2mg or placebo for the 8 weeks. SBP at the end of the 8 weeks was compared with placebo and the baxdrostat 2mg dose. Long-term safety is assessed at the end of the 52 weeks compared to a standard of care arm.

Additional confirmatory secondary endpoints include the effect of baxdrostat versus placebo on seated SBP at week 12 in the resistant hypertension subpopulation, the effect of baxdrostat versus placebo on seated diastolic blood pressure at week 12, and proportion of participants achieving seated SBP less than 130 mmHg at week 12. Occurrence of adverse events was also evaluated.

Baxdrostat

Baxdrostat is a potential first-in-class, highly selective and potent, oral, small molecule that inhibits aldosterone synthase,¹⁰ an enzyme encoded by the CYP11B2 gene, which is responsible for the synthesis of aldosterone in the adrenal gland.³ In clinical trials, baxdrostat was observed to significantly lower aldosterone levels without affecting cortisol levels across a wide range of doses.^11,12 Baxdrostat is currently being investigated in clinical trials as a monotherapy for hypertension^9,13,14 and primary aldosteronism,¹⁵ and in combination with dapagliflozin for chronic kidney disease^16,17 and hypertension, and the prevention of heart failure in patients with hypertension.¹⁸

AstraZeneca acquired baxdrostat through its purchase of CinCor Pharma, Inc. in February 2023.¹⁹ A contingent value right of $10 per share in cash ($0.5 billion) is payable to former CinCor shareholders upon the submission of a new drug application either in the US or Europe.¹⁹

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.

References

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2. Carey RM, et al. Prevalence of apparent treatment-resistant hypertension in the United States: comparison of the 2008 and 2018 American Heart Association scientific statements on resistant hypertension [including online supplement]. Hypertension. 2019;73(2):424-431.
3. Cannavo A, et al. Aldosterone and mineralocorticoid receptor system in cardiovascular physiology and pathophysiology. Oxid Med Cell Longev. 2018;2018:1204598.
4. Inoue K, et al. Serum aldosterone concentration, blood pressure, and coronary artery calcium: the Multi-Ethnic Study of Atherosclerosis [including online supplement]. Hypertension. 2020;76(1):113-120.
5. Ettehad, D. et al. Blood pressure lowering for prevention of cardiovascular disease and death: a systematic review and meta-analysis; Lancet 2016;387:957–67.
6. McEvoy JW, et al. 2024 ESC Guidelines for the management of elevated blood pressure and hypertension. EurHeart J. 2024;45(38):3912-4018.
7. Whelton PK, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Hypertension. 2018;71(6):1269-1324.
8. 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.
9. 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 August 2025.
10. Bogman K, et al. Preclinical and early clinical profile of a highly selective and potent oral inhibitor of aldosterone synthase (CYP11B2). Hypertension. 2017;69:189-96.
11. 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)108–118.
12. Freeman MW, et al. Phase 2 Trial of Baxdrostat for Treatment-Resistant Hypertension. NEJM. 2023;388:395-405.
13. 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 August 2025.
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 (BaxAsia). Available at: https://clinicaltrials.gov/study/NCT06344104. Accessed August 2025.
15. 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 August 2025.
16. 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 August 2025.
17. 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 August 2025.
18. ClinicalTrials.gov. A Phase III Study Investigating Heart Failure and Cardiovascular Death With Baxdrostat in Combination With Dapagliflozin (Prevent-HF). ClinicalTrials.gov identifier: NCT06677060. Available at: https://clinicaltrials.gov/study/NCT06677060. Accessed August 2025.
19. AstraZeneca 2023. Acquisition of CinCor Pharma complete. Available at: https://www.astrazeneca.com/media-centre/press-releases/2023/astrazeneca-acquires-cincor-for-cardiorenal-asset.html. Accessed August 2025.

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