AstraZeneca's Aldosterone Inhibitor Baxdrostat Effective Against Resistant HTN in Late-Stage Trial

Baxdrostat, a highly selective aldosterone synthase inhibitor (ASI) that blocks CYP11B2, significantly lowered systolic blood pressure (SBP) in adults with uncontrolled or treatment-resistant hypertension, meeting the primary and all secondary endpoints in the phase 3 BaxHTN trial, AstraZeneca announced on July 14. At 12 weeks, study participants receiving baxdrostat at either 2 mg or 1 mg once daily had statistically significant and clinically meaningful reductions in mean seated SBP compared with placebo, on top of standard of care therapy. The investigational and potentially first-in-class oral medication also demonstrated favorable safety and tolerability, according to the AstraZeneca statement.

For the multicenter randomized, double-blind, and placebo-controlled study, 796 participants were randomly assigned to receive baxdrostat 2 mg, 1 mg, or placebo. The primary endpoint was the difference in mean change from baseline in seated SBP at week 12. Additional secondary endpoints in BaxHTN included the effect on seated SBP at week 12 in the study's resistant hypertension subpopulation, seated diastolic BP, the percentage of participants achieving SBP of 130 mm Hg or less, and safety outcomes.

The study included a persistence-of-effect analysis during an 8-week randomized withdrawal period (weeks 24 to week 32). During that period, approximately 300 participants receiving baxdrostat 200 mg were rerandomized to either continue on that dose or on placebo for the 8 weeks. According to AstraZeneca, baxdrostat's long-term safety is being assessed compared to a standard of care arm at 52 weeks.

“Many people continue to struggle with high blood pressure that is hard to control, even when taking multiple medications,” primary investigator Bryan Williams, MD, chair of medicine at University College London, said in the statement. “The highly promising BaxHTN phase III 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.”

Hypertension affects an estimated 1.3 billion people globally. In the US, BP among roughly half of adults who are receiving multiple antihypertensive agents remains uncontrolled. Aldosterone dysregulation has emerged as a key biological driver in patients with hard-to-treat hypertension.

The ASI inhibitor blocks CYP11B2, the enzyme responsible for aldosterone synthesis. It has been shown in clinical trials to lower aldosterone without affecting cortisol, across a range of doses. It is also in development for primary aldosteronism and in combination with dapagliflozin for chronic kidney disease and cardiovascular risk reduction in adults with hypertension. .

“These [BaxHTN] 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,” Sharon Barr, executive vice president, biopharmaceuticals R&D at AstraZeneca, said.

The company will present the BaxHTN results during a late-breaking Hot Line session at the 2025 European Society of Cardiology Congress.