Baxdrostat: Current Status for Resistant Hypertension and Primary Aldosteronism
Baxdrostat is a novel aldosterone synthase inhibitor that has shown promising results in phase 2 trials for resistant hypertension but is still undergoing phase 3 clinical trials and is not yet FDA-approved or endorsed by major guidelines for routine clinical use. 1
Current Development Status
Baxdrostat represents a new therapeutic approach targeting aldosterone synthesis, which is particularly relevant for patients with resistant hypertension and primary aldosteronism. The drug works by selectively inhibiting aldosterone synthase, thereby reducing aldosterone production.
Clinical Trial Results
- The BrigHTN phase 2 trial showed promising results with dose-dependent reductions in systolic blood pressure in patients with resistant hypertension 2
- However, the HALO trial did not demonstrate blood pressure-lowering benefits compared to placebo 2
- Currently, multiple phase 3 trials are underway to further evaluate efficacy and safety:
- BaxHTN (NCT06034743) - evaluating patients with uncontrolled or resistant hypertension
- BaxAsia (NCT06344104) - focusing on Asian populations with uncontrolled or resistant hypertension
- Bax24 (NCT06168409) - specifically studying patients with resistant hypertension 3
Guideline Recognition
The 2024 European Society of Cardiology (ESC) guidelines acknowledge baxdrostat as a novel aldosterone synthase inhibitor that has significantly lowered blood pressure in patients with uncontrolled hypertension in phase 2 trials, but do not yet recommend its routine use pending cardiovascular outcomes trials 1.
Potential Clinical Applications
Resistant Hypertension
Resistant hypertension affects approximately 20% of hypertensive patients and is defined as blood pressure that remains above goal despite concurrent use of 3 or more antihypertensive medications of different classes (including a diuretic) at optimal doses, or requiring 4 or more medications to achieve control 1.
Current guidelines recommend mineralocorticoid receptor antagonists (MRAs) like spironolactone as the preferred fourth-line agent for resistant hypertension 1, 4. Baxdrostat may eventually offer an alternative approach by directly inhibiting aldosterone synthesis rather than blocking its receptor.
Primary Aldosteronism
Primary aldosteronism affects approximately 20% of patients with resistant hypertension 1 and is often underdiagnosed, with only about 2% of at-risk patients being formally tested 5.
Current treatment options for primary aldosteronism include:
- Laparoscopic adrenalectomy for unilateral disease
- MRAs (spironolactone or eplerenone) for bilateral disease 4, 5
Baxdrostat could potentially offer a new treatment option by targeting the underlying pathophysiology of excess aldosterone production.
Practical Considerations
Patient Selection
If baxdrostat eventually receives regulatory approval, it would likely be positioned for:
- Patients with resistant hypertension not adequately controlled on current regimens
- Patients with primary aldosteronism who cannot tolerate MRAs due to side effects
- Patients with elevated aldosterone levels contributing to hypertension
Monitoring
Based on its mechanism of action, monitoring would likely include:
- Blood pressure response
- Serum potassium levels
- Renal function
- Adrenal hormone profiles
Future Outlook
The ongoing phase 3 trials will provide critical information about:
- Efficacy in larger and more diverse patient populations
- Long-term safety profile
- Sustained blood pressure-lowering effects
- Potential impact on cardiovascular and renal outcomes
Until these trials are completed and regulatory approval is obtained, current guideline-recommended therapies should continue to be used for resistant hypertension and primary aldosteronism.
Key Takeaways
- Baxdrostat represents a novel approach to treating hypertension by selectively inhibiting aldosterone synthesis
- While showing promise in early trials, it remains investigational and is not yet approved for clinical use
- Current guidelines acknowledge its development but await outcomes data before making recommendations
- Ongoing phase 3 trials will determine its place in the treatment algorithm for resistant hypertension and primary aldosteronism