Kidney Week

Abstract: SA-PO353

Effect of Baxdrostat on Albuminuria in Treatment-Resistant Hypertension

Session Information

• Hypertension, CVD, and the Kidneys: Clinical Research
  October 26, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Hypertension and CVD

• 1602 Hypertension and CVD: Clinical

Authors

• Heerspink, Hiddo Jan L., University Medical Center Groningen, Groningen, Netherlands

Hiddo Jan L. Heerspink, PhD

• Little, Dustin J., AstraZeneca Biopharmaceuticals R and D, Warsaw, Poland

Dustin J. Little, MD

• Myte, Robin, AstraZeneca Biopharmaceuticals R and D, Warsaw, Poland

Robin Myte, PhD

• Zaozerska, Nataliia, AstraZeneca Biopharmaceuticals R and D, Warsaw, Poland

Nataliia Zaozerska

• Menzies, Robert I., AstraZeneca Biopharmaceuticals R and D, Gothenburg, Sweden

Robert I. Menzies, PhD

• Perl, Shira, AstraZeneca Biopharmaceuticals R and D, Warsaw, Poland

Shira Perl, MD

• Chertow, Glenn M., Stanford University School of Medicine, Stanford, California, United States

Glenn M. Chertow, MD, MPH, FASN

• Dwyer, Jamie P., University of Utah Health, Salt Lake City, Utah, United States

Jamie P. Dwyer, MD

Background

Baxdrostat is an aldosterone synthase inhibitor in development in combination with the sodium glucose cotransporter 2 (SGLT2) inhibitor dapagliflozin for patients with CKD and hypertension (HTN). We performed a post hoc analysis evaluating baxdrostat’s effect on urine albumin-to-creatinine ratio (UACR) in a phase 2 study in participants with resistant HTN.

Methods

BrigHTN was a randomized, placebo-controlled trial where qualifying participants with resistant hypertension (defined as treatment with at least 3 anti-hypertensive drugs, at least one of which was a diuretic) were randomized 1:1:1:1 to baxdrostat 0.5, 1, or 2 mg or placebo for 12 weeks. We analyzed geometric mean change from baseline to 12 weeks of log-transformed UACR and calculated the percent change within and between randomized groups. We excluded missing values (n=83).

Results

Overall, 275 participants were randomized of whom 39 (14.2%) had baseline eGFR <60 mL/min/1.73m² and 60 (21.8%) had UACR >30 mg/g. Baseline median UACR was 12 mg/g with quartile 1 and quartile 3 values of 6 and 36 mg/g, respectively. As reported previously, baxdrostat 1 mg and 2 mg resulted in statistically significant placebo-adjusted reductions in systolic blood pressure. All baxdrostat groups showed placebo-adjusted reductions in UACR (Table 1); changes in the baxdrostat 2 mg group met conventional levels of statistical significance (p=0.011).

Conclusion

In a placebo-controlled trial of baxdrostat for resistant hypertension, baxdrostat 2 mg daily reduced UACR. Relatively few BrigHTN participants had CKD, and any amount of albuminuria was allowed. The phase 3 Arctic trial (NCT06268873) of patients with CKD and hypertension will compare baxdrostat/dapagliflozin to placebo/dapagliflozin both on top of maximally tolerated ACE inhibitors or angiotensin receptor blockers to assess the primary endpoint of change in eGFR over time.

Funding

• Commercial Support – AstraZeneca