AstraZeneca’s Baxfendy becomes first aldosterone synthase inhibitor approved for hypertension in US

Edited by Robert McTiernan··3 min read

AstraZeneca (LSE/STO/NYSE: AZN) has received US FDA approval for Baxfendy (baxdrostat), making it the first aldosterone synthase inhibitor cleared for the treatment of hypertension in adults not adequately controlled on existing antihypertensive therapy. The drug is approved for use in combination with other antihypertensive medications.

Baxfendy is an oral, small-molecule inhibitor of aldosterone synthase, the enzyme encoded by the CYP11B2 gene responsible for aldosterone production in the adrenal gland. By selectively blocking this enzyme, baxdrostat reduces circulating aldosterone levels without affecting cortisol, targeting a hormonal driver of persistently elevated blood pressure upstream of the mineralocorticoid receptor. AstraZeneca acquired the asset through its purchase of CinCor Pharma in February 2023, which had in-licensed baxdrostat from Roche in 2019.

The approval was based on data from the BaxHTN Phase III trial (NCT06034743), a double-blind, placebo-controlled study enrolling 796 adults with uncontrolled or resistant hypertension on two or more antihypertensive agents, including a diuretic. The primary endpoint was the change from baseline in mean seated systolic blood pressure (SBP) at week 12. At the 2 mg dose, baxdrostat reduced seated SBP by 15.7 mmHg from baseline, with a placebo-adjusted reduction of 9.8 mmHg (95% CI, -12.6 to -7.0; p<0.001). The 1 mg dose produced a placebo-adjusted reduction of 8.7 mmHg (95% CI, -11.5 to -5.8; p<0.001). Results were consistent across both the uncontrolled and treatment-resistant subgroups. Full results were published in the New England Journal of Medicine. The drug was reported to be generally well-tolerated with no unanticipated safety findings.

The selectivity of baxdrostat for CYP11B2 over the closely related CYP11B1 enzyme, which governs cortisol synthesis, has been a central feature of the compound’s clinical development. Earlier aldosterone synthase inhibitor programs were limited by off-target suppression of cortisol, which constrained their therapeutic use. In clinical trials, baxdrostat was observed to lower aldosterone levels across a wide dose range without affecting cortisol, a profile that distinguishes it from prior compounds in this mechanistic class and supports its tolerability.

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Approval context

The hypertension treatment landscape for patients who remain uncontrolled despite multiple agents has seen limited therapeutic innovation for approximately two decades, according to AstraZeneca. Approximately 50% of US patients already taking multiple antihypertensive medications continue to have persistently elevated blood pressure, the company said, citing published prevalence data. The most direct regulatory comparator is Tryvio (aprocitentan), a dual endothelin receptor antagonist developed by Idorsia Pharmaceuticals and approved by the FDA in March 2024 for hypertension not adequately controlled in combination with other antihypertensives — an indication with near-identical label language. The two drugs act through distinct mechanisms, with aprocitentan targeting vasoconstriction via endothelin receptor blockade rather than aldosterone biosynthesis.

Within the same mechanistic class, Mineralys Therapeutics has submitted an NDA for lorundrostat, also a selective aldosterone synthase inhibitor, with an FDA PDUFA target action date of December 22, 2026. If approved, lorundrostat would represent a same-class competitor to baxdrostat in the resistant and uncontrolled hypertension population.

AstraZeneca is also investigating baxdrostat across a broader cardiorenal program. Active Phase III trials include studies in primary aldosteronism, chronic kidney disease in combination with dapagliflozin, and heart failure prevention, reflecting the company’s positioning of aldosterone synthase inhibition as a platform mechanism across conditions where elevated aldosterone contributes to organ damage.

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