Results from the BaxHTN phase III trial showed baxdrostat (AstraZeneca)—a highly selective aldosterone synthase inhibitor (ASI)—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 uncontrolled and resistant hypertension who received baxdrostat or placebo on top of standard of care.
The data were presented in a hot line session at the 2025 European Society of Cardiology (ESC) congress (29 August–1 September, Madrid, Spain) and also simultaneously published in the New England Journal of Medicine.
Baxdrostat met the primary and secondary endpoints in the 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 15.7mmHg (95% confidence interval [CI], -17.6 to -13.7) and placebo-adjusted reduction was 9.8mmHg (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 hyperkalaemia (>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. 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.
“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,” Bryan Williams (University College London, London, UK), the trial’s primary investigator, was quoted as saying in a press release from AstraZeneca These data show that aldosterone plays a greater role in hard-to-control hypertension than previously recognised, 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.”
