Positive results from the BaxHTN Phase-III trial show that Baxdrostat, an investigational drug developed by AstraZeneca, achieved statistically significant and clinically meaningful reductions in Systolic Blood Pressure (SBP) in patients with hard-to-control hypertension. The findings were presented at the European Society of Cardiology (ESC) Congress 2025 in Madrid and published simultaneously in the New England Journal of Medicine.

Baxdrostat met the primary and all secondary endpoints in the BaxHTN phase-III 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 15.7 mmHg (95 percent confidence interval [CI], -17.6 to -13.7) and placebo-adjusted reduction was 9.8 mmHg (95 percent 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 percent CI, -16.5 to -12.5) and placebo-adjusted reduction was 8.7 mmHg (95 percent CI, -11.5 to -5.8; p<0.001). The reduction in mean seated SBP with placebo was 5.8 mmHg (95 percent 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 percent each]) compared with placebo (0.0 percent). 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. Baxdrostat 2mg showed durable long-term reductions in SBP, while both doses reduced diastolic blood pressure and nearly tripled the odds of patients achieving target SBP <130 mmHg versus placebo.

In a pre-specified exploratory analysis of a subgroup of patients, Baxdrostat reduced 24-hour and ambulatory nighttime SBP compared with placebo, key indicators of SBP control and reduced cardiovascular risk. The 2mg dose lowered 24-hour SBP by 16.9 mmHg (95 percent CI, -25.6 to -8.3), and the pooled 2mg and 1mg doses lowered nighttime SBP by 11.7 mmHg (95 percent CI, -19.5 to -3.8). The Bax24 phase-III trial, evaluating 24-hour ambulatory effects, is expected to read out later this year.

Primary investigator Dr Bryan Williams, Chair – Medicine, University College London, said, “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. These data show that aldosterone plays a greater role in hard-to-control hypertension than previously 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.”

Hypertension affects 1.3 billion people worldwide, with about 50 per cent of the US patients failing to achieve blood pressure control despite multiple therapies. Aldosterone dysregulation is increasingly recognised as a driver of the disease and associated cardiovascular and renal risks. Evidence shows that lowering SBP by just 10 mmHg can cut the risk of major cardiovascular events by roughly 20 per cent, underscoring the need for new targeted therapies.

Sharon Barr, Executive Vice President, BioPharmaceuticals R&D, said, “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. We look forward to advance 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.”

AstraZeneca acquired baxdrostat through its purchase of CinCor Pharma in February 2023. The drug is currently being investigated in clinical trials as a monotherapy for hypertension and primary aldosteronism, and in combination with dapagliflozin for chronic kidney disease and the prevention of heart failure in hypertensive patients.