Breakthrough Clinical Results
Positive results from the BaxHTN Phase III trial demonstrated that baxdrostat, a highly selective aldosterone synthase inhibitor, significantly reduced systolic blood pressure in patients with hard-to-control hypertension. The 2mg dose lowered systolic blood pressure by 15.7 mmHg (9.8 mmHg placebo-adjusted), meeting primary and secondary endpoints. The drug was generally well-tolerated with a manageable safety profile. These findings, presented at the European Society of Cardiology Congress 2025 and published in the New England Journal of Medicine, highlight baxdrostat's potential as a first-in-class treatment for this challenging condition affecting millions worldwide. AstraZeneca plans to advance regulatory filings for baxdrostat.
Key Highlights
- Statistically significant and clinically meaningful reduction in systolic blood pressure (SBP) in patients with hard-to-control hypertension.
- Baxdrostat met primary and all secondary endpoints in the BaxHTN Phase III trial.
- Generally well-tolerated with no unanticipated safety findings.
- Potential first-in-class treatment for hard-to-control hypertension.
Incidence and Prevalence
Global Estimates of Hypertension Incidence and Prevalence
Hypertension stands as the leading cause of deaths worldwide, contributing to approximately 30% of all deaths. The World Health Organization has identified hypertension as the major factor responsible for the most deaths worldwide, accounting for 12.8% per year or more than seven million deaths. It ranks third on the list of factors responsible for the burden of disease during life, as measured by disability-adjusted life-years.
As the biggest single risk factor for global deaths, hypertension is an important precursor and the most common risk factor of heart failure. The total number of patients with hypertension is expected to grow as the population ages. In Asia, the proportion of the elderly population aged 65 years or more is projected to increase from 7.4% in 2015 to 10.9% in 2030. Notably, half of the cases of Cardiovascular Disease (CVD) are estimated to occur in Asia, the world's most populous continent, where hypertension results in more deaths than any other cardiovascular risk factors.
Recent epidemiological data reveals significant variations in hypertension prevalence across different populations. A meta-analysis indicates that the pooled prevalence of hypertension among the general population in high-altitude areas is 33.0% (95% CI: 29.0-38.0%). Tibetan individuals were more prone to developing hypertension at high altitudes, with a prevalence of 41% compared to 18% in non-Tibetan individuals living in the Himalayas and Pamir Mountains.
The crude incidence rate of hypertension, per 1000 person-years, varies significantly by ethnicity: 56.8 for whites, 84.9 for blacks, 65.7 for Hispanics, and 52.2 for Chinese according to the Multi-Ethnic Study of Atherosclerosis. Blacks had a higher incidence of hypertension compared with whites between 45 and 74 years of age but not after age 75 years. Similarly, Hispanic participants also had a higher incidence of hypertension compared with whites.
Recent studies show concerning trends in specific populations. In Chinese college students (233,603 participants), the overall prevalence of hypertension was 3.3% (95% CI=2.9%-3.6%), with higher rates in males (6.2%) than females (1.1%). This prevalence showed an increasing trend from 2010 to 2020, with predictions reaching 10% by 2030 and 14.6% by 2040.
Environmental factors, socioeconomic status, and lifestyle choices significantly influence hypertension risk. Severe noise exposure is associated with hypertension development (hazard ratio: 1.28). Studies in Ethiopia found hypertension prevalence of 14.4% among university employees, while research in Western India revealed 7.5% of adolescent school children had hypertension. In the Russian Federation, deterioration of social living conditions was associated with higher hypertension prevalence among men (OR=1.18) and elderly people (OR=1.16).
These statistics underscore the growing global burden of hypertension, with significant variations across geographic regions, ethnicities, and socioeconomic factors.
Study Design Parameters
Study Design Parameters and Endpoints in Key Hypertension Trials
Study Designs
Key hypertension trials primarily utilize randomized controlled trials (RCTs), including phase 2/3, 3, or 4 trials. Double-blind randomized studies are common, particularly dose-ranging studies (phase II) and comparative studies (phase III). Other designs include observational studies, prospective cohort studies, Markov models, systematic reviews and meta-analyses, and cluster-randomized feasibility trials. Some trials employ multicenter parallel randomized designs or prospective, observational, cluster-based, parallel-group approaches.
Study Populations
Trials typically include hypertensive outpatients with varying degrees of severity. Some focus on older participants (≥60 years) or specific populations like patients with type 2 diabetes and microalbuminuria. Inclusion criteria commonly specify elevated blood pressure (≥130/85 mmHg), while some exclude patients with proven secondary hypertension. The representativeness of trial populations remains a concern, as trials report substantially fewer serious adverse events than expected from community rates.
Interventions
Common interventions include renin-angiotensin system (RAS) inhibitors (ACE inhibitors, ARBs, renin inhibitors), calcium channel blockers (CCBs), thiazide diuretics, beta-blockers, and single-pill combinations (e.g., perindopril/indapamide). Some trials compare early vs. late treatment initiation strategies or different blood pressure targets (e.g., <120 mmHg vs. <140 mmHg).
Primary Endpoints
Key primary endpoints include: - All-cause mortality/death - Cardiovascular events including fatal and non-fatal stroke, myocardial infarction (MI), and congestive heart failure (CHF) - End-stage renal failure (ESRF) - Blood pressure measurements including systolic (SBP) and diastolic (DBP) pressures using mercury sphygmomanometer, automatic devices, or 24-hour ambulatory blood pressure measurements (ABPM) - Percentage of patients achieving BP control (typically <140/90 mmHg) - Functional independence measured by scales like the modified Rankin scale
Secondary Endpoints
Secondary endpoints often include: - Quality-adjusted life years (QALY) - Life expectancy (LE) - Time to onset of ESRF - Heart rate (HR) - Serious adverse events - Medication adherence - Cost outcomes and cost savings - Quality of Life measured by instruments like the WHOQoL-BREF - Exercise capacity
Measurement Methods
Blood pressure is typically recorded after at least 5 minutes of rest in the sitting position at 1-3 minute intervals. Measurements often involve three consecutive readings to obtain an average. Some trials use blinded measure of systolic BP as the primary outcome.
Follow-up Duration
Trials typically have a minimum follow-up of six months, with many extending to 1 year or longer. Some economic analyses project outcomes over 25 years. Assessment points commonly include baseline, 12 months, and 36 months for longer studies.
Baxdrostat Clinical Trials Beyond Hypertension
Based on the available information, baxdrostat (also known as CIN-107) is currently only being evaluated for hypertension-related indications. Specifically, it is being studied as a potential treatment for treatment-resistant hypertension and uncontrolled hypertension.
As a selective aldosterone synthase inhibitor, baxdrostat targets the production of aldosterone, which is associated with inflammation, systemic hypertension, and organ fibrosis that contribute to adverse cardiovascular events.
The clinical trials mentioned in the available information include:
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The BrigHTN trial (Phase 2) - This study showed promising results demonstrating the efficacy of baxdrostat for hypertension.
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The HALO trial - This study did not demonstrate any blood pressure-lowering benefit of baxdrostat when compared with placebo.
Currently, several additional studies are underway to evaluate the effectiveness of baxdrostat as an anti-hypertensive agent.
There is no information available about: - Clinical trials of baxdrostat for non-hypertension indications - Intervention models for trials beyond hypertension - Specific trial designs, dosing regimens, or intervention protocols for any non-hypertension uses
The research focus appears to remain on baxdrostat's potential as a treatment for hypertension, particularly in patients who have not responded adequately to other anti-hypertensive medications.