Baxdrostat New Drug Application accepted under FDA Priority Review in the US for patients with hard-to-control hypertension

AstraZeneca’s New Drug Application (NDA) for baxdrostat has been accepted for Priority Review by the US Food and Drug Administration (FDA) in the US for the treatment of adult patients with hard-to-control (uncontrolled or treatment resistant) hypertension as an add-on to other antihypertensive medicines when these do not provide adequate lowering of blood pressure.

The Prescription Drug User Fee Act (PDUFA) date is anticipated during the second quarter of 2026 following use of a Priority Review voucher.

There are 1.4 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 is increasingly recognised as a key driver of hard-to-control hypertension, contributing to elevated cardiovascular and renal risk.^3,4

Sharon Barr, Executive Vice President, BioPharmaceuticals R&D, said: “This Priority Review demonstrates our commitment to advancing baxdrostat as a potential first- and best-in-class aldosterone synthase inhibitor for the millions of people living with hard-to-control hypertension as quickly as possible. The substantial reduction in systolic blood pressure seen in the BaxHTN trial underscores baxdrostat’s novel mechanism of action and its potential to bring innovation to a disease area that has seen limited progress in over two decades.”

The NDA is based on data from the BaxHTN Phase III trial⁵ which was presented during a Hot Line session at the European Society of Cardiology (ESC) Congress 2025 and simultaneously published in the New England Journal of Medicine.⁶

The trial showed that baxdrostat, on top of standard of care, met the primary and all secondary endpoints. Standard of care consisted of a stable regimen of two antihypertensive agents at baseline, one of which is a diuretic (uncontrolled hypertension) or more than three antihypertensive agents at baseline, one of which is a diuretic (treatment-resistant hypertension).⁶ At week 12, the change from baseline and placebo-adjusted change from baseline reductions in mean seated SBP were 15.7 mmHg (95% confidence interval [CI], -17.6 to -13.7) and 9.8 mmHg (95% CI, -12.6 to -7.0; p less than 0.001) for the 2mg dose, and 14.5 mmHg (95% CI, -16.5 to -12.5) and 8.7 mmHg (95% CI, -11.5 to -5.8; p less than 0.001) for the 1mg dose, respectively. The results were consistent across both uncontrolled and treatment-resistant subgroups.⁶

Baxdrostat was generally well tolerated with a safety profile consistent with its mechanism of action. There were no unanticipated safety findings, and most adverse events were mild.⁶

Baxdrostat is a potential first-in-class, highly selective aldosterone synthase inhibitor (ASI) designed to lower blood pressure by specifically inhibiting the production of aldosterone, a key hormone that raises blood pressure and increases the risk of heart and kidney problems. Baxdrostat is currently being investigated in clinical trials enrolling more than 20,000 patients globally, as a monotherapy for hypertension^5,7,8 and primary aldosteronism,⁹ and in combination with dapagliflozin for chronic kidney disease^10,11 and the prevention of heart failure in high-risk patients.¹²

Notes

Hard-to-control hypertension

Hypertension is a medical condition characterised by consistently high blood pressure levels, affecting an estimated 1.4 billion people worldwide.^1,13,14 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.^13,14 An observational study of nearly 60,000 patients studied over a median of 9.7 years showed that a 9.5 mmHg increase in SBP was associated with a 30% increase in risk of all-cause mortality and 41% increase in risk of cardiovascular death.¹⁵ Studies have shown that increased night-time blood pressure is associated with higher cardiovascular risk,^15,16 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.^17,18

Hard-to-control (uncontrolled and resistant) hypertension remains a major public health challenge.¹⁹ 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.² Uncontrolled hypertension refers to persistently elevated blood pressure despite the use of two or more medications, while rHTN, a more severe form, remains elevated despite treatment with three or more medications.^13,14

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,²⁰ are strongly associated with poor blood pressure control. When left untreated, hypertension significantly increases the risk of cardiovascular and kidney-related complications.^13,14

BaxHTN trial

The BaxHTN Phase III trial⁵ 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 characterised 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 randomised withdrawal period from week 24 to week 32. Approximately 300 patients treated with baxdrostat 2mg were re-randomised 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,²¹ an enzyme encoded by the CYP11B2 gene, which is responsible for the synthesis of aldosterone in the adrenal gland.⁴ In clinical trials, baxdrostat was observed to significantly lower aldosterone levels without affecting cortisol levels across a wide range of doses.^22,23 Baxdrostat is currently being investigated in clinical trials as a monotherapy for hypertension^5,7,8 and primary aldosteronism,⁹ and in combination with dapagliflozin for chronic kidney disease and hypertension,^10,11 and the prevention of heart failure in patients with hypertension.¹²

AstraZeneca acquired baxdrostat through its purchase of CinCor Pharma, Inc. in February 2023.²⁴ A contingent value right of $10 per share in cash ($0.5 billion) was paid to former CinCor shareholders upon the submission of an NDA to the FDA.²⁴

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. Please visit astrazeneca.com and follow the Company on Social Media @AstraZeneca.

References

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