Baxdrostat Reduces Systolic Blood Pressure in Uncontrolled, Treatment-Resistant Hypertension

Baxdrostat, an aldosterone synthase inhibitor, demonstrated clinically meaningful and statistically significant reductions in mean seated systolic blood pressure (SBP) at 2 doses compared with placebo at 12 weeks in patients with uncontrolled or treatment-resistant hypertension, according to a news release from AstraZeneca. These reductions were observed in the multicenter, randomized, double-blind, placebo-controlled phase 3 BaxHTN clinical trial (NCT06034743).^1,2

Hypertension, called "the silent killer," can significantly increase cardiovascular risk. | Image Credit: © thodonal - stock.adobe.com

A potential first-in-class, potent, highly selective oral small molecule drug, baxdrostat is designed to inhibit aldosterone synthase, which is responsible for synthesizing aldosterone in the adrenal gland. Aldosterone is a key contributor to hypertension that increases blood pressure by promoting sodium and water retention. When aldosterone levels are elevated in the body, blood pressure becomes much harder to control and can significantly increase the risk of cardiovascular events such as stroke or heart attack.^1,5

Numerous clinical trials have observed significant lowering of aldosterone levels through baxdrostat use, without impacting cortisol levels. Until now, data from an extensive phase 3 study had not been reported.^1,4

BaxHTN Demonstrates Significant Reductions in SBP

BaxHTN featured 3 components, working synergistically to achieve the primary efficacy end point of mean change from baseline in SBP at week 12 between individuals treated with baxdrostat—in doses of 2 mg or 1 mg separately—or placebo. In total, 796 participants were randomly assigned to receive baxdrostat 2 mg, 1 mg, or placebo once daily. Importantly, these treatments were initiated on top of a patient’s standard care. Efficacy persistence was examined during a randomized withdrawal period from week 24 to week 32, according to the investigators.¹

To be included in the trial, patients with uncontrolled hypertension must have been treated with 2 different antihypertensive medications. For patients with resistant hypertension, patients must have been treated with 3 or more different antihypertensive medications, of which one must be a diuretic, the authors explained.¹

Although detailed study results were not released—AstraZeneca intends to present the data during a session at the European Society of Cardiology Congress in August 2025—the authors noted that baxdrostat meaningfully reduced mean seated SBP compared with placebo at 12 weeks. Furthermore, the trial met all key secondary end points. Regarding safety, baxdrostat was generally well-tolerated among BaxHTN participants, with a favorable safety profile reported by the investigators.¹

“Many people continue to struggle with high blood pressure that is hard to control, even when taking multiple medications,” Bryan Williams, MD, chair of medicine at University College London and primary investigator on BaxHTN, said in the news release. “The highly promising BaxHTN phase [3] results show that once-daily baxdrostat on top of standard of care can meaningfully lower systolic blood pressure and offer a potential new treatment approach for controlling hypertension, the leading risk factor for cardiovascular disease.”¹

Baxdrostat’s Potentially Expansive Role in Cardiovascular Prevention

Hypertension is primarily characterized by sustained and high blood pressure levels, which can, over time, damage vital organs and blood vessels, heightening the risk of severe health complications. Though many various antihypertensive medications are available, difficult-to-control hypertension has remained a complex disease for providers to effectively treat. This is in part because many patients have difficulty achieving their blood pressure goals.^1,5

Baxdrostat has major potential to transform the treatment paradigm for hard-to-treat, uncontrolled hypertension if clinical trials of the agent continue to elicit positive results. Beyond hypertension, baxdrostat is being investigated for a series of related indications, including primary aldosteronism, for the prevention of heart failure in hypertensive patients, and as part of a combination regimen to treat chronic kidney disease. By targeting aldosterone, baxdrostat could become an effective treatment for a wide range of cardiovascular indications.¹

“We are very excited with the BaxHTN phase 3 results, which show statistically significant and clinically meaningful reductions in systolic blood pressure,” Sharon Barr, executive vice president of BioPharmaceuticals research and development, said in the news release. “These findings provide compelling evidence of baxdrostat’s potential to address a critical unmet need by targeting aldosterone dysregulation, bringing a novel mechanism to a field that has seen little innovation in over two decades.”¹

REFERENCES

1. AstraZeneca. Baxdrostat met the primary and all secondary endpoints in BaxHTN Phase III trial in patients with uncontrolled or treatment resistant hypertension. News Release. Released July 14, 2025. Accessed July 31, 2025. https://www.astrazeneca-us.com/media/press-releases/2025/baxdrostat-met-the-primary-and-all-secondary-endpoints-in-BaxHTN-Phase-III-trial-in-patients-with-uncontrolled-or-treatment-resistant-hypertension.html

2. Jansen SL, Malesker MA, Hilleman DE. Hypertension: A silent killer requiring novel therapies. Pharmacy Times. Accessed July 19, 2025. Published July 31, 2025. https://www.pharmacytimes.com/view/hypertension-a-silent-killer-requiring-novel-therapies

3. Cannavo A, Bencivenga L, Liccardo D, et al. Aldosterone and Mineralocorticoid Receptor System in Cardiovascular Physiology and Pathophysiology. Oxid Med Cell Longev. 2018:1204598. doi:10.1155/2018/1204598

4. Bogman K, Schwab D, Delporte ML, et al. Preclinical and Early Clinical Profile of a Highly Selective and Potent Oral Inhibitor of Aldosterone Synthase (CYP11B2). Hypertension. 2016;69(1). doi:10.1161/HYPERTENSIONAHA.116.07716

5. McEvoy JW, McCarthy CP, Bruno RM, et al. 2024 ESC Guidelines for the management of elevated blood pressure and hypertension: Developed by the task force on the management of elevated blood pressure and hypertension of the European Society of Cardiology (ESC) and endorsed by the European Society of Endocrinology (ESE) and the European Stroke Organisation (ESO). Euro Heart J. 2-24;45(38):3912-4018. doi:10.1093/eurheartj/ehae178