Baxdrostat, a new hypertension medication undergoing Phase 2 trials, was not associated with a reduction in blood pressure when compared to placebo in patients with resistant hypertension, according to results from the newly released HALO trial.
The role of hypertension and adverse health outcomes has been well established in the medical literature. Concerningly, an estimated 10 million Americans suffer from “treatment resistant hypertension,” or uncontrolled blood pressure despite at least three blood-pressure lowering medications (Carey et al). The need for pharmacotherapy in this population is critical, explained a speaker at 2023 American College of Cardiology (ACC) Scientific Session.
Dr. Deepak Bhatt, MD, MPH, the Director of Mount Sinai Heart, described the results of the HALO trial, a phase 2 randomized controlled trial evaluating the efficacy of baxdrostat at the ACC Scientific Session in New Orleans, LA. Resistant hypertension has been strongly linked to the renin-angiotensin-aldosterone system, with observational data demonstrating the role of aldosterone excess in contributing to high blood pressure. Prior randomized controlled trials (PATHWAY-2) and metanalyses showed that mineralocorticoid receptor antagonists (MRAs), which block the effect of aldosterone, were among the most effective medications at reducing blood pressure (Yugar Toledo et al). This led to significant excitement when baxdrostat, a selective aldosterone synthase inhibitor, was shown to cause a sustained, dose-dependent reduction in plasma aldosterone levels in a Phase 1 trial. Additionally, baxdrostat reduced systolic blood pressure in patients with resistant hypertension by 11 mm Hg when compared to placebo in a separate Phase 2 study, BrigHTN (Freeman et al).
The HALO trial enrolled a total of 249 patients across multiple centers, evaluating the impact of three different doses of baxdrostat against placebo after 8 weeks of therapy in patients with uncontrolled hypertension. Ultimately, the trial did not achieve its primary endpoint, and there was no statistically significant reduction in blood pressure between baxdrostat and placebo. The results were limited by a large placebo effect and low adherence to baxdrostat at specific sites (Bhatt et. al). Despite the negative result of the trial, optimism remains regarding the novel medication.
“We have not had a new anti-hypertensive class of drugs in well over a decade,” added Dr. Nanette Wenger, an ACC panelist and Professor Emerita at Emory University School of Medicine in Atlanta GA. “As we look at this drug, we say – this is another [sic] potential either to add to a regimen for with patients with resistant hypertension, or should it be shown to be effective, possibly even as an upstream drug for patients with hypertension.”
“Baxdrostat appeared to have a generally favorable safety profile and was well tolerated,” concluded Dr. Bhatt, commenting that “my prediction is in the resistant hypertension population, where there is such a large unmet need, [baxdrostat] will end up being a useful addition to the armamentarium.”
Dr. Aravind Kalluri is a resident at the Hospital of the University of Pennsylvania and served as a CardioNerds Conference Scholar for the American College of Cardiology 2023 Scientific Sessions.