FDA approves baxdrostat, the first aldosterone synthase inhibitor for hypertension

## What was approved Baxdrostat is a small-molecule inhibitor of CYP11B2, the enzyme that produces aldosterone in the adrenal cortex. By blocking aldosterone synthesis at the source, the drug differs from spironolactone and eplerenone, which sit one step downstream and antagonise the mineralocorticoid receptor. The agency cleared it for adults with hypertension that is inadequately controlled despite a stable background regimen. ## The trial BaxHTN was a 12-week, placebo-controlled Phase 3 study in 796 adults with hypertension uncontrolled on a multi-drug background that included a diuretic. Participants received 1 mg or 2 mg of baxdrostat once daily, or placebo. The primary endpoint was change in seated systolic blood pressure at week 12. ## The result At 2 mg, systolic blood pressure fell by 15.7 mmHg from baseline, which translates to a placebo-adjusted reduction of 9.8 mmHg. The 1 mg arm produced a smaller but statistically significant drop. Diastolic blood pressure followed the same direction. The full 95% confidence intervals appear in the FDA label. ## Safety Hyperkalemia (potassium ≥5.5 mmol/L) occurred in 6.6% of patients on 1 mg and 10.2% on 2 mg, against a placebo rate near 1%. Hyponatremia rates were 2.1% on 1 mg and 3.2% on 2 mg. Both signals are mechanism-consistent and warrant repeat potassium and sodium checks during the first weeks of therapy. ## What this means for you If you sit in the resistant hypertension category, defined as office blood pressure above 130/80 despite three antihypertensive drugs at full dose including a diuretic, baxdrostat is now a fourth-line option. It is not a first-line drug. The cleaner mechanism appeals to men who tolerate spironolactone poorly because of gynecomastia and reduced libido, both driven by spironolactone's off-target binding at the androgen receptor. ## Caveats The 12-week primary endpoint measured blood pressure, not cardiovascular events. A larger cardiovascular outcomes trial is underway and not yet read out. Cost will be substantial relative to generic spironolactone.