Baxdrostat for Resistant Hypertension Meets Primary Endpoints in BAX24 Phase 3 Clinical Trial

Baxdrostat, a novel aldosterone synthase inhibitor, met its primary endpoint in the phase 3 Bax24 trial, demonstrating statistically significant reductions in 24-hour ambulatory systolic blood pressure (SBP) compared with placebo in 218 adults with treatment-resistant hypertension. ¹

The trial showed the investigational drug's efficacy throughout the 24-hour period, including during early morning hours when cardiovascular event risk peaks. BAX24 participants were randomly assigned to receive baxdrostat 2 mg or placebo once daily on top of standard care. The positive high-level results were reported today in a press release from developer AstraZeneca.¹

Approximately 50% of US adults receiving multiple antihypertensive medications fail to achieve blood pressure control.² Treatment-resistant hypertension, defined as elevated blood pressure despite treatment with 3 or more medications, affects a substantial subset of the 1.4 billion people worldwide living with hypertension.³ Multiple studies have established that 24-hour blood pressure measurements predict cardiovascular events more accurately than clinic-based readings.⁴ A 9.5 mmHg rise in 24-hour average systolic blood pressure is associated with a 30% increase in all-cause mortality risk.⁴

"The Bax24 results show that a once-daily baxdrostat regimen can deliver highly clinically meaningful reductions in 24-hour systolic blood pressure, including in the morning when patients are at greater risk of heart attack and stroke," Bryan Williams, MD, chair of medicine at University College London and the study's primary investigator, said in a statement.¹ "These results are groundbreaking and together with the BaxHTN results mean we have the potential to change our treatment approach for the many patients whose hypertension remains uncontrolled despite current therapies."¹

Baxdrostat selectively inhibits aldosterone synthase, an enzyme encoded by the CYP11B2 gene responsible for aldosterone synthesis in the adrenal gland, according to AstraZeneca.¹ Phase I studies showed the drug reaches peak blood levels within 2 to 4 hours and maintains a half-life of approximately 26 to 30 hours.⁵ Clinical trials have demonstrated that baxdrostat significantly lowers aldosterone levels without affecting cortisol across a wide dose range.⁵

"This second phase 3 trial of baxdrostat shows substantial improvement in blood pressure, which reflects its durable half-life of up to 30 hours and highly selective inhibition of aldosterone synthase. Too many patients today have hypertension that remains hard-to-control throughout the day and night, making them especially vulnerable to cardiac events," Sharon Barr, AstraZeneca executive vice president, biopharmaceuticals R&D, said in the statement. "We are advancing our regulatory filings and rapidly progressing our robust clinical development programme for baxdrostat, as both a mono- and combination-therapy, across additional conditions where aldosterone plays a key role, including primary aldosteronism, chronic kidney disease and heart failure prevention."¹

Baxdrostat was generally well tolerated, with a safety profile consistent with the earlier BaxHTN trial.⁶ The Bax24 study randomly assigned participants to receive baxdrostat or placebo once daily, with the primary efficacy endpoint measuring change from baseline in ambulatory 24-hour average SBP at week 12, AstraZeneca stated. Secondary endpoints included changes in night-time and daytime ambulatory SBP, seated SBP, the proportion of participants achieving 24-hour average SBP below 130 mm Hg, and those achieving nocturnal SBP dipping greater than 10% at week 12.¹

Elevated aldosterone, along with factors including obesity, high salt intake, and various genetic or secondary conditions, is strongly associated with poor blood pressure control.⁸ Research confirms that increased night-time blood pressure is associated with higher cardiovascular risk.⁸ Further, individuals with hypertension face elevated cardiovascular event risk during morning blood pressure surges.⁸

AstraZeneca plans to share the BAX24 data with regulatory authorities globally and will present findings at the American Heart Association Scientific Sessions in November 2025. The company currently is investigating baxdrostat as monotherapy for hypertension and primary aldosteronism, and in combination with dapagliflozin for chronic kidney disease, and heart failure prevention in high-risk individuals.

References

1. Baxdrostat met the primary endpoint in Bax24 Phase III trial in patients with resistant hypertension. News release. AstraZeneca. October 7, 2025. Accessed October 7, 2025. https://www.astrazeneca.com/media-centre/press-releases/2025/baxdrostat-met-the-primary-endpoint-in-bax24-phase-iii-trial-in-patients-with-resistant-hypertension.html
2. Carey RM, et al. Prevalence of Apparent Treatment-Resistant Hypertension in the United States. Hypertension. 2019;73(2):424-431.
3. World Health Organization. Global report on hypertension 2025: high stakes: turning evidence into action. 2025. Accessed October 7, 2025. https://iris.who.int/handle/10665/382841.
4. 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.
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   5 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. Accessed September 2025.
6. Halsey G. AstraZeneca's Aldosterone Inhibitor Baxdrostat Effective Against Resistant HTN in Late-Stage Trial. Patient Care. July 14, 2025. Accessed October 7, 2025. https://www.patientcareonline.com/view/astrazeneca-s-aldosterone-inhibitor-baxdrostat-effective-against-resistant-htn-in-late-stage-trial
7. 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.
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