Topline Findings
- Baxdrostat Significantly Lowers Blood Pressure: Phase III BaxHTN trial results showed placebo-adjusted reductions of –8.7 mmHg for 1-mg and –9.8 mmHg for 2-mg doses in patients with hard-to-control hypertension.
- High Rates of Blood Pressure Control: Nearly 40% of patients receiving baxdrostat achieved target systolic blood pressure below 130 mmHg compared with 18.7% on placebo, highlighting its potential for resistant hypertension.
- Manageable Safety Profile: Baxdrostat was generally well tolerated, with mild adverse events (AEs), supporting its safety for patients on multiple antihypertensive therapies.
Results from the Phase III BaxHTN trial (NCT06034743) showed that AstraZeneca’s baxdrostat demonstrated promise in addressing hard-to-control hypertension. According to the company, baxdrostat at both 2 mg and 1 mg doses delivered statistically significant and clinically meaningful reductions in mean seated systolic blood pressure compared with placebo at 12 weeks, particularly in patients already on standard therapies.1
How Effectively Does Baxdrostat Reduce Blood Pressure in Patients with Hard-to-Control Hypertension?
“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,” said primary trial investigator Bryan Williams, chair of medicine, University College London, in a press release. “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.”
BaxHTN Trial Design and Endpoints
- The randomized, double-blind, placebo-controlled, parallel-group BaxHTN trial evaluated the safety and efficacy of baxdrostat in 796 patients with hard-to-control hypertension.
- Patients were randomly assigned in a 1:1:1 ratio to receive baxdrostat 2mg, 1mg, or placebo once daily.
- The primary endpoint of the trial was the difference in mean change from baseline in seated systolic blood pressure (SBP) at week 12 between patients treated with baxdrostat and placebo.
- Key secondary endpoints included change from baseline in seated SBP for 2 mg baxdrostat, change from baseline in seated SBP for 1 mg baxdrostat, change from baseline in seated diastolic blood pressure for 2 mg baxdrostat, and achieving seated SBP < 130 mmHg for 2 mg baxdrostat.
- From there, efficacy durability was evaluated during a randomized withdrawal phase from week 24 to week 32, in which about 300 patients on baxdrostat 2 mg were re-randomized in a 2:1 ratio to continue treatment or switch to placebo, and systolic blood pressure was compared between groups after eight weeks.1,2
- Results showed that at week 12, baxdrostat produced robust, statistically significant reductions in systolic blood pressure compared with placebo, with placebo-adjusted differences of –8.7 mmHg for the 1 mg dose and –9.8 mmHg for the 2 mg dose.
- A total of 39.4% of patients on 1 mg baxdrostat and 40% on 2 mg baxdrostat achieved target systolic blood pressure below 130 mmHg versus 18.7% on placebo.
- During the randomized withdrawal period, patients continuing on 2 mg baxdrostat maintained a 3.7 mmHg reduction, while those switched to placebo experienced an increase of 1.4 mmHg.
Safety and Tolerability
- Baxdrostat was generally well tolerated, with most adverse events (AEs) classified as mild.
- Serious AEs occurred in 1.9% of patients who received 1 mg, 3.4% who received 2 mg, and 2.7% of those in the placebo group.3
Broader Context
According to AstraZeneca, hypertension affects an estimated 1.3 billion people globally, and in the United States, roughly half of patients on multiple therapies still fail to achieve adequate blood pressure control. A 10 mmHg reduction in systolic blood pressure can reduce major cardiovascular event risk by approximately 20%.1
“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,” said Sharon Barr, EVP, BioPharmaceuticals R&D, AstraZeneca, in a press release. “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 programme across indications where aldosterone plays a key role, including chronic kidney disease and heart failure prevention.”
References
- 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. AstraZeneca. August 30, 2025. Accessed September 3, 2025. https://www.astrazeneca.com/media-centre/press-releases/2025/baxdrostat-demonstrated-statistically-significant-clinically-meaningful-reduction-sbp-patients-hard-control-hypertension-baxhtn-phase-iii-trial.html
- 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). Clinicaltrials.gov. Accessed September 3, 2025. https://clinicaltrials.gov/study/NCT06034743?term=BaxHTN%20&rank=1
- Efficacy and Safety of Baxdrostat in Uncontrolled and Resistant Hypertension. The New England Journal of Medicine. Accesssed September 3, 2025. https://www.nejm.org/doi/full/10.1056/NEJMoa2507109?logout=true
