HALO Trial: Baxdrostat is Well-Tolerated, But Misses Mark in Uncontrolled Hypertension

Data from the HALO trial are providing further insight into the effects of baxdrostat use on blood pressure in individuals with hypertension.

Presented at the American College of Cardiology’s (ACC) 2023 Annual Scientific Session Together With the World Congress of Cardiology, the trial represents the second phase 2 study of baxdrostat and suggests the agent was well-tolerated but failed to achieve its primary endpoint of a statistically significant change in mean seated blood pressure versus placebo at 8 weeks.

Just 4 months earlier, at the American Heart Association 2022 Scientific Sessions, the phase 2 BrigHTN trial provided evidence baxdrostat, a highly selective, once daily, oral small molecule inhibitor of aldosterone synthase, was well-tolerated and associated with dose-dependent changes in systolic blood pressure of −20.3 mmHg, −17.5 mmHg, and −12.1 mmHg were observed in the trials the 2 mg, 1 mg, and 0.5 mg groups, respectively, with the placebo group experiencing a mean change in systolic blood pressure of -9.4 mmHg. In the BrigHTN trial, which included 248 participants who completed the study, was conducted among a population of patients with treatment-resistant hypertension, which was defined as a blood pressure of 130/80 mmHg or higher and receiving stable doses of at least 3 antihypertensive agents, including a diuretic.²

The HALO trial data presented at ACC 2023 by Deepak Bhatt, MD, MPH, director of Mount Sinai Heart, who also presented the BrigHTN data, provided even further insight into the effects of baxdrostat use, with a trial population of patients with uncontrolled hypertension despite use of 1 or 2 antihypertensives at maximally tolerated doses. . HALO enrolled a population of 249 patients, with 64, 63, 62, and 60 patients randomized to placebo, 0.5 mg baxdrostat, 1 mg baxdrostat, and 2 mg baxdrostat, respectively.¹

For inclusion in the trial, patients were required to have a mean seated systolic blood pressure of 140 mmHg or greater. Inclusion criterion also required patients to be on a stable regimen of an ACE inhibitor or an ARB, an ACEi/ARB plus a thiazide diuretic, or an ACEi/ARB plus a calcium channel blocker.

The primary endpoint of interest for thetrial was change from baseline in mean seated systolic blood pressure after 8 weeks of treatment. Secondary endpoints of interest for the trial included changes in diastolic blood pressure, aldosterone, and renin levels.

Upon analysis, results indicated the primary endpoint of placebo-corrected systolic blood pressure change was not met with any of the baxdrostat doses, with investigators noting a large mean change in systolic blood pressure in the placebo group of -16.6 mmHg. Analyses of safety data from the trial demonstrated 1 patient experienced a serious adverse event in the 1 mg baxdrostat group and 1 patient in the 2 mg baxdrostat group, with investigators noting one serious adverse event was acute respiratory failure following a diagnosis of COVID-19.¹

In his presentation, Bhatt noted multiple limitations within the study to consider, including suboptimal adherence, a modest population size, and assessment of the primary endpoint at 8 weeks rather than at 12 weeks, which was the procedure in the BrigHTN trial.

For more on the results of this trial and what is next for baxdrostat, we sat down with Bhatt on the floor at ACC 2023.

References

1. Bhatt DL, Halvorsen Y-D, Marshall W, et al. American College of Cardiology 72nd Annual Scientific Sessions. In: A Study of CIN-107 in Patients With Uncontrolled Hypertension.
2. Freeman MW, Halvorsen Y-D, Marshall W, et al. Phase 2 trial of baxdrostat for treatment-resistant hypertension. New England Journal of Medicine. 2023;388(5):395-405. doi:10.1056/nejmoa2213169

Deepak L. Bhatt, MD, MPH, receives research funding from CinCor Pharma, Inc. and AstraZeneca.