A major international phase 3 clinical trial has reported that baxdrostat, an investigational aldosterone synthase inhibitor, offers significant blood-pressure reduction for patients with uncontrolled or resistant hypertension. The multinational, double-blind, randomized, placebo-controlled study evaluated 796 adults whose systolic blood pressure remained between 140 mm Hg and just under 170 mm Hg despite being on at least two antihypertensive drugs, or three or more drugs including a diuretic. Following a two-week placebo run-in phase, 794 participants were assigned to receive either 1 mg of baxdrostat, 2 mg of baxdrostat, or a placebo once daily for 12 weeks.
By the end of the trial period, baxdrostat demonstrated marked superiority over placebo. The 1-mg dose reduced seated systolic blood pressure by 14.5 mm Hg, and the 2-mg dose by 15.7 mm Hg, compared with a 5.8-mm Hg drop in the placebo group. The resulting placebo-corrected reductions of 8.7 mm Hg for the 1-mg dose and 9.8 mm Hg for the 2-mg dose were both statistically significant, highlighting the drug’s strong antihypertensive effect. Safety data indicated that hyperkalemia, a known risk associated with aldosterone-targeting therapies, occurred infrequently. Elevated potassium levels above 6.0 mmol/L were observed in 2.3% of patients receiving the 1-mg dose, 3% of those on the 2-mg dose, and 0.4% of placebo recipients, suggesting an acceptable safety profile with appropriate monitoring. These findings are supported by earlier research, including a study by Freeman et al., which also reported dose-dependent blood pressure reductions in patients with treatment-resistant hypertension treated with baxdrostat.
Investigators noted that baxdrostat may offer several advantages over existing treatments for resistant hypertension. Its selectivity in inhibiting aldosterone synthesis, rather than blocking aldosterone receptors, allows it to avoid many hormonal side effects commonly associated with mineralocorticoid receptor antagonists such as spironolactone and eplerenone, including gynecomastia and menstrual irregularities. Early evidence indicates that baxdrostat may also have fewer off-target effects than older agents that affect multiple steroid-hormone pathways, improving overall tolerability. The drug showed meaningful blood-pressure reductions even in patients already taking multiple antihypertensive medications a challenging population in whom further therapeutic gains are often difficult to achieve.
The study findings underscore baxdrostat’s potential as a novel therapeutic tool for difficult-to-control hypertension, a condition linked to increased risks of stroke, heart failure, and chronic kidney disease. Investigators concluded that adding baxdrostat to standard therapy produced significant and clinically relevant improvement in blood pressure in patients who typically struggle to meet treatment targets. If approved, baxdrostat may become one of the first highly selective aldosterone synthase inhibitors available for clinical use, offering a promising new option for patients with resistant hypertension and potentially reshaping the treatment landscape.
Reference
- Flack JM, Azizi M, Brown JM, Dwyer JP, Fronczek J, Jones ESW et al., Efficacy and Safety of Baxdrostat in Uncontrolled and Resistant Hypertension. N Engl J Med. 2025 Oct 9;393(14):1363-1374.
- Freeman MW, Halvorsen YD, Marshall W, Pater M, Isaacsohn J, Pearce C et al,. Phase 2 Trial of Baxdrostat for Treatment-Resistant Hypertension. N Engl J Med. 2023 Feb 2;388(5):395-405.