Key takeaways
- Baxdrostat’s success in BaxHTN underscores the importance of novel mechanisms: Targeting aldosterone dysregulation represents a long-awaited innovation in hypertension trials and may shift first-line treatment strategies for resistant cases.
- Trial design featured a well-executed randomized withdrawal phase: This design element not only demonstrated durability of effect but also offers a model for evaluating sustained efficacy in future late-phase studies.
- Operational complexity was well-managed across multiple patient subgroups: Coordinating enrollment and data across uncontrolled and treatment-resistant populations, while maintaining adherence to placebo-controlled standards, highlights strong trial execution practices.
AstraZeneca has shared positive results from the Phase III BaxHTN clinical trial (NCT06034743) of baxdrostat in patients with uncontrolled or treatment resistant hypertension. The small molecule inhibitor achieved a statistically significant and clinically meaningful reduction in mean seated systolic blood pressure (SBP). The trial also met all key secondary endpoints.1
Baxdrostat significantly reduces systolic blood pressure
According to BaxHTN data, treatment with baxdrostat on top of standard of care achieved this reduction in mean SBP at 12 weeks compared to placebo. Results were positive across two different doses of 2 mg and 1 mg. Additionally, baxdrostat was generally well tolerated with a favorable safety profile.
In a press release, Bryan Williams, MD, chair of medicine at University College London, primary investigator, said: “Many people continue to struggle with high blood pressure that is hard to control, even when taking multiple medications. 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.”
Study design and patient population
The Phase III BaxHTN trial is a multicenter, randomized, double-blinded, placebo-controlled, parallel group study to evaluate the safety, tolerability, and effect of baxdrostat.
- Baxdrostat was evaluated in patients with uncontrolled hypertension being treated with two different antihypertensive medications, and patients with resistant hypertension being treated with three or more different antihypertensive medications, one being a diuretic
- The study enrolled 796 patients, randomized equally (1:1:1) to receive baxdrostat 2 mg, 1 mg, or placebo once daily.
- The primary endpoint evaluated the change in SBP from baseline at week 12 between baxdrostat (each dose) and placebo.
Durability and long-term safety
A randomized withdrawal phase assessed durability of effect from week 24 to week 32, where ~300 patients on baxdrostat 2 mg were re-randomized 2:1 to either continue treatment or switch to placebo.
- SBP at the end of this 8-week withdrawal period was compared between those continuing baxdrostat 2 mg and those switched to placebo.
- Long-term safety is being evaluated over 52 weeks, with comparisons made to a standard of care control group.
- Secondary endpoints include SBP change in the resistant hypertension subgroup, change in seated diastolic blood pressure, proportion of patients reaching seated SBP <130 mmHg, and incidence of adverse events across treatment arms.
In the press release, Sharon Barr, executive vice president, biopharmaceuticals R&D, AstraZeneca, added: “We are very excited with the BaxHTN Phase III results, which show statistically significant and clinically meaningful reductions in systolic blood pressure. 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.”
Previous study data support ongoing development
In 2022, the New England Journal of Medicine published results from another study of baxdrostat (NCT04519658) in patients with treatment resistant hypertension. In this Phase II, multicenter, placebo-controlled trial, baxdrostat showed substantial decreases in blood pressure.2
In 248 patients who completed the trial, dose-dependent changes in SBP of −20.3 mmHg, −17.5 mmHg, −12.1 mmHg, and −9.4 mmHg were observed in the 2 mg, 1 mg, 0.5 mg, and placebo groups, respectively. The study was actually stopped early due to overwhelming efficacy in the primary endpoint.
“Our trial showed substantial decreases in blood pressure when patients with treatment-resistant hypertension who were receiving stable doses of at least three antihypertensive medications also received the selective aldosterone synthase inhibitor baxdrostat,” the study authors wrote. “The reduction in blood pressure was associated with a decrease in the plasma aldosterone level and a compensatory increase in plasma renin activity, without a reduction in the cortisol level.”
References
1. Baxdrostat met the primary and all secondary endpoints in BaxHTN Phase III trial in patients with uncontrolled or treatment resistant hypertension. News release. AstraZeneca. July 14, 2025. Acessed 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. Mason W. Freeman, et al. Phase 2 Trial of Baxdrostat for Treatment-Resistant Hypertension. New England Journal of Medicine. https://www.nejm.org/doi/full/10.1056/NEJMoa2213169 (2022).
