CinCor’s experimental therapy baxdrostat is in development to treat conditions including high blood pressure and chronic kidney disease by blocking the production of aldosterone, an important hormone that contributes to hypertension.
Investigators reported that baxdrostat – at several dose levels – reduced plasma aldosterone levels but not cortisol levels in results from the recent BrigHTN study (ClinicalTrials.gov NCT04519658). Participants with treatment-resistant hypertension (people with blood pressure of 130/80 mmHg or higher receiving stable doses of at least three antihypertensive agents, including a diuretic) received baxdrostat (0.5 mg, 1 mg, or 2 mg) or placebo once daily for 12 weeks. The study’s primary endpoint was improvement in systolic blood pressure in each baxdrostat-dose group as compared with the placebo group.
Mechanism of action
Baxdrostat targets aldosterone synthase, encoded by the CYP11B2 gene. Importantly, the drug has low affinity for the the enzyme responsible for cortisol synthesis, which is also encoded by the CYP11B1 gene. This means that, as demonstrated in several clinical trials to date, baxdrostat significantly lowers aldosterone levels without affecting the body’s cortisol levels. High levels of cortisol can negatively affect the body in many ways, including raising blood pressure.
Phase 1 trials
The safety, tolerability, pharmacokinetics and pharmacodynamics of baxdrostat in healthy volunteers has been investigated in multiple Phase 1 clinical trials. No serious adverse events or treatment-emergent adverse events leading to treatment withdrawal associated with baxdrostat in those trials. In a Phase 1 clinical trial conducted in subjects with varying degrees of renal function, one serious adverse event unrelated to baxdrostat was observed.
Phase 2 trials
In the Phase 2 BrigHtn study, patients with treatment-resistant hypertension who received varying doses of baxdrostat showed a statistically significant lowering of systolic blood pressure. The results of this study were published in the New England Journal of Medicine in Nov. 2022 and include Cardiometabolic Health Congress (CMHC) faculty member Deepak L. Bhatt, MD, MPH, as a co-author. Currently, baxdrostat is being studied in four other Phase 2 clinical trials:
- HALO: A study evaluating multiple dose strengths of baxdrostat in patients with uncontrolled hypertension
- OLE: An extension of the HALO study to evaluate long-term use of baxdrostat
- FigHtn-CKD: A dose-range study examining baxdrostat use in patients with uncontrolled hypertension and chronic kidney disease
- Spark-PA: An evaluation of the safety, tolerability, and effectiveness of baxdrostat for the management of blood pressure in patients with primary aldosteronism
The maker of baxdrostat is acquired by AstraZeneca
Pharmaceutical and biotechnology giant AstraZeneca announced in Jan. 2023, that it would acquire U.S.-based company CinCor, the drug developer who makes baxdrostat. Experts say the deal and subsequent acquisition of baxdrostat will complement AstraZeneca’s interest in expanding their development of therapies for cardiorenal diseases.
“The CinCor management team has laid very important scientific and clinical groundwork for the baxdrostat program, including the successful Phase 2 BrigHtn trial that was recently published in the New England Journal of Medicine. On behalf of CinCor’s Board of Directors, I would like to recognize and thank the CinCor team, scientific advisors and patients for their dedication and contributions to the advancement of the development of baxdrostat.” – James Healy, chair of CinCor’s board of directors