Baxdrostat May Lower Systolic BP in CKD With Uncontrolled Hypertension

A phase 2 trial finds that baxdrostat, an aldosterone synthase inhibitor, meaningfully reduces systolic blood pressure (SBP) in patients with chronic kidney disease (CKD) and uncontrolled hypertension.

Recently, in the phase 3 BaxHTN trial, baxdrostat demonstrated efficacy in general patients with uncontrolled hypertension on 2 or more antihypertensive medications, including some with resistant hypertension. Results were published in the New England Journal of Medicine.

In the phase 2 FigHTN trial (NCT05432167), all patients had stage 2-4 CKD. Baxdrostat demonstrated a significant placebo-corrected reduction in systolic BP of -8.1 mmHg (95% confidence interval -13.4 to -2.8 mm Hg, P=0.003) over 26 weeks, Jamie Dwyer, MD, of the University of Utah at Salt Lake City, and colleagues reported in the Journal of the American Society of Nephrology. Baxdrostat was well tolerated in the CKD population.

The FigHTN trial enrolled patients with a mean seated office SBP of 140-180 mmHg or 130-180 mmHg with type 2 diabetes (80% of patients) at baseline, despite 86% taking 2 or more antihypertensive medications. All had an estimated glomerular filtration rate (eGFR) of 25 to 75 mL/min per 1.73 m² and a urinary albumin to creatinine ratio (UACR) of 100 mg/g or greater. All were currently taking an angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) at the maximum tolerated daily dose.

Investigators randomly assigned 195 patients to receive placebo or baxdrostat at a low-dose (0.5 mg titrated up to 1 mg) or high-dose (2 mg titrated up to 4 mg) for 26 weeks. Mean age was 66 years, and the US cohort included White, Black, and Asian patients, including a third with Hispanic ethnicity.

The trial’s secondary end point assessed this change by baxdrostat dose. SBP significantly decreased -9.0 mmHg (-15.1 to -2.9; P=0.004) in the low-dose baxdrostat group and -7.2 mmHg (-13.2 to -1.2; P=0.02) in the high-dose group, compared with placebo.

In the pooled baxdrostat group, UACR decreased by 55% compared with placebo. After an expected eGFR dip with baxdrostat, eGFR stabilized with a modest difference compared with placebo at 26 weeks: -2.3 vs -1.8 mL/min/1.73 m², respectively.

Treatment-emergent adverse event (TEAEs) were experienced by 78% of the baxdrostat pooled group and 55% of the placebo group. Hyperkalemia was the most frequent TEAE affecting 41% of the baxdrostat pooled group and 5% of the placebo group. Serum potassium exceeding 6.0 mg/dL affected 2% vs 0%, respectively. At least one serious adverse event was reported by 9% vs 3%, respectively. TEAE leading to drug discontinuation affected 16% vs 8%, respectively. Neither deaths nor adrenal insufficiency occurred. Baxdrostat does not meaningfully interfere with cortisol synthesis, according to previous research.

“Baxdrostat is currently being studied in combination with dapagliflozin in two Phase 3 double-blind randomized controlled trials for participants with CKD and hypertension,” Dr Dwyer’s team revealed. “NCT06268873 is evaluating baxdrostat/dapagliflozin in CKD progression (eGFR slope), while NCT06742723 is assessing the effect of baxdrostat/dapagliflozin on cardiovascular and kidney events. In addition, NCT06677060 will evaluate baxdrostat/dapagliflozin in lowering the risk of cardiovascular mortality and incident heart failure (with and without CKD).” 

Disclosure: This research was supported by AstraZeneca. Please see the original reference for a full list of disclosures.