Baxdrostat cuts BP in patients with resistant hypertension in phase 2 trial
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CHICAGO — Baxdrostat, an aldosterone synthase inhibitor, yielded substantial dose-related decreases in BP in patients with treatment-resistant hypertension, according to results from the phase 2 BrigHtn trial.
The BrigHtn trial met its primary endpoint, demonstrating a significant change from baseline to 12 weeks in mean seated systolic BP: –20.3 mm Hg with once-daily baxdrostat (CinCor Pharma) 2 mg, –17.5 mm Hg with 1 mg, –12.1 mm Hg with 0.5 mg and –9.4 mm Hg with placebo, according to data presented at the American Heart Association Scientific Sessions.
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The difference in change in systolic BP was –11 mm Hg between the 2 mg and placebo groups (P < .001) and –8.1 mm Hg between the 1 mg and placebo groups (P = .003).
Change in mean seated diastolic BP was –14.3 mm Hg with the 2 mg dose, –11.8 mm Hg with the 1 mg dose, –8.6 mm Hg with the 0.5 mg dose and –9.2 mm Hg with placebo, and the difference between the 2 mg and placebo groups was –5.2 mm Hg (P = .004), the researchers reported.
“Two milligrams baxdrostat significantly and substantially reduced systolic and diastolic blood pressure in patients with treatment-resistant hypertension,” Mason W. Freeman, MD, chief medical officer at CinCor Pharma, said during a late-breaking science presentation.
Baxdrostat is a highly selective, oral small molecule inhibitor of aldosterone synthase, the enzyme responsible for the synthesis of aldosterone in the adrenal gland. This therapy is in development for populations with significant unmet needs, including treatment-resistant hypertension and primary aldosteronism, according to a press release issued by CinCor Pharma.
“For over 60 years, clinicians have been using medications that lower plasma aldosterone activity in order to lower blood pressure. For at least 20 years, medicinal chemists have tried to create a novel drug that would lower aldosterone levels directly by inhibiting the synthesis of the hormone in order to avoid some of the potential troublesome or serious adverse events that come from the use of mineralocorticoid receptor agonists,” Freeman said during the presentation. “Baxdrostat, in preclinical studies, managed to accomplish this ... showing that ... it could block aldosterone.”
The BrigHtn trial enrolled 248 patients who were randomly assigned once-daily oral placebo or one of three doses of baxdrostat for 12 weeks. All patients had treatment-resistant hypertension, which was defined as elevated BP despite at least three antihypertensive agents, including a diuretic. Patients enrolled were aged in their early 60s and the population was predominantly white (70%). Freeman said there was a sizable proportion of patients who identified as Black or Hispanic/Latino. The findings were simultaneously published in The New England Journal of Medicine.
Freeman said baxdrostat demonstrated a favorable safety profile and was well tolerated. There were no deaths during the trial period and the researchers did not attribute any serious adverse events to the study drug. No instances of adrenocortical insufficiency occurred. Two patients had baxdrostat-related increases in potassium of 6 mmol/L or greater; however, following withdrawal and reinitiation of the study drug, the increases in potassium did not recur, according to the results.
In other results, baxdrostat produced dose-dependent reductions in aldosterone, increased plasma renin activity and did not reduce cortisol.
“Baxdrostat reduced aldosterone levels and also increased plasma renin activity in exactly the way that you would expect a drug made to lower aldosterone levels would produce,” Freeman said. “We have beautiful biomarker evidence of not only blood pressure lowering but the mechanism by which that blood pressure lowering is occurring.
“We think these data suggest that baxdrostat has the potential to treat diseases associated with aldosterone excess including hypertension and primary aldosteronism,” Freeman said.
There will be additional phase 2 studies in patients with chronic kidney disease to further explore the risk for hyperkalemia and the phase 3 program will begin in 2023, according to Freeman.
References:
- Freeman MW, et al. N Engl J Med. 2022;doi:10.1056/NEJMoa2213169.
- CinCor Pharma announces late-breaking presentation of phase 2 BrigHtn data on baxdrostat in treatment-resistant hypertension at the 2022 American Heart Association Scientific Sessions. www.cincor.com/news-releases/news-release-details/cincor-pharma-announces-late-breaking-presentation-phase-2-0. Published Nov. 7, 2022. Accessed Nov. 7, 2022.
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Freeman MW, et al. LBS.09: Resistant Hypertension: A Pressure Cooker. Presented at: American Heart Association Scientific Sessions; Nov. 5-7, 2022; Chicago (hybrid meeting).
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