Baxdrostat Meets Efficacy Endpoint in Phase 3 Trial for Resistant Hypertension

Baxdrostat, a potential first-in-class aldosterone synthase inhibitors (ASI) for the treatment of difficult-to-control hypertension, has achieved the primary endpoint of statistically significant systolic blood pressure (SBP) reduction in its phase 3 BaxHTN trial.1

Announced by parent company AstraZeneca on July 14, 2025, the results of BaxHTN indicate the potential of baxdrostat to lower aldosterone content, preventing dysregulation, which has been cited as a leading cause of hypertension. Uncontrolled hypertension was defined as being persistent despite lifestyle changes and/or the use of ≥2 medications, while resistant hypertension remains elevated despite ≥3 treatments.1

“Many people continue to struggle with high blood pressure that is hard to control, even when taking multiple medications,” said Bryan Williams, MD, chair of medicine at University College London, and the primary investigator in BaxHTN. “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.”1

Baxdrostat is a highly selective and potent oral small molecule that inhibits ASI, an enzyme responsible for the synthesis of aldosterone in the adrenal gland. Baxdrostat significantly reduced aldosterone levels without impacting cortisol levels in a range of doses during prior trials.1

BaxHTN consisted of 3 components supporting the primary efficacy endpoint of difference in mean change from baseline in seated SBP at the end of a 12-week, double-blind, placebo-controlled period. Patients were randomized in a 1:1:1 ratio to receive baxdrostat 2mg, 1mg, or placebo once daily. Efficacy persistence was analyzed through a randomized withdrawal period from Week 24 to 32. Roughly 300 patients treated with baxdrostat 2mg were randomized in a 2:1 ratio to either receive baxdrostat 2mg or placebo for the 8 weeks; SDP at the end of this period was compared with placebo and the baxdrostat 2mg dose group. Long-term safety was assessed at the end of Week 52 compared to a standard of care arm.1

BaxHTN was commenced after positive results from phase 2 trials in 2022 and 2023, coined BrigHTN and HALO, respectively. The former indicated an association between baxdrostat and an 11 mmHg placebo-adjusted SDP decline without impacting cortisol levels. The 12-week study included 275 patients, with 248 completing the trial; no serious adverse events were attributed to baxdrostat.2

However, the HALO trial in 2023 failed to achieve its endpoint of placebo-corrected SBP change in any of the 3 baxdrostat doses (.5mg, 1mg, and 2mg). Investigators noted several limitations, including a relatively small population, suboptimal adherence, and assessment of the primary endpoint at 8 rather than 12 weeks. HALO did indicate similar safety data to BrigHTN, noting only 2 of 248 patients experienced serious adverse events.3

In their press release, AstraZeneca described plans to present data from the BaxHTN trial in a late-breaking Hot Line session at the European Society of Cardiology Congress in August of 2025 and will share the results with regulatory authorities worldwide.1

“We are very excited with the BaxHTN Phase III results, which show statistically significant and clinically meaningful reductions in systolic blood pressure,” said Sharon Barr, executive vice president of BioPharmaceuticals R&D. “These 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.”1

References

1. Baxdrostat met the primary and all secondary endpoints in BaxHTN Phase III trial in patients with uncontrolled or treatment resistant hypertension. AstraZeneca. July 14, 2025. Accessed July 14, 2025. https://www.astrazeneca.com/media-centre/press-releases/2025/baxdrostat-met-primary-and-all-secondary-endpts-in-baxhtn-phiii-trial.html

2. Phase 2 Data Shows Promise for Baxdrostat in Treatment-Resistant Hypertension. HCPLive. November 7, 2022. Accessed July 14, 2025. https://www.hcplive.com/view/phase-2-data-shows-promise-for-baxdrostat-in-treatment-resistant-hypertension

3. Campbell P. HALO Trial: Baxdrostat is Well-Tolerated, But Misses Mark in Uncontrolled Hypertension. HCPLive. March 7, 2023. Accessed July 14, 2025. https://www.hcplive.com/view/halo-trial-baxdrostat-is-well-tolerated-but-misses-mark-in-uncontrolled-hypertension