New drug, baxdrostat, offers hope to patients resistant to high blood pressure treatment: Phase 2 trial
The highest dose of oral medication (Baxdrostat) in patients with treatment-resistant hypertension reduced blood pressure by 20 points.
UK: A new class of drugs may offer hope to millions of people affected by uncontrolled high blood pressure, according to results from a phase II trial. The results were produced in The New England Journal of Medicine (NEJM) on November 7, 2022, and presented at the 2022 Scientific Sessions conference of the American Heart Association.
Baxdrostat can substantially reduce high blood pressure in patients who may not respond to traditional treatments for the condition (hypertension). The oral medication targets a hormone involved in regulating the amount of salt in the body.
It works by preventing the production of aldosterone in the body. The drug suppressed urine and blood levels of aldosterone. The study demonstrated that Baxdrostat causes a marked fall in blood pressure in patients with treatment-resistant hypertension. This type of hypertension, in part, is due to excess aldosterone production. Aldosterone leads to salt retention in the body, raising blood pressure. Patients with excessive aldosterone levels are resistant to treatment with the commonly used hypertension drugs.
Aldosterone synthase controls aldosterone production and, for several decades, has been a pharmacologic target for hypertension treatment. Selective aldosterone synthase inhibition is essential but is challenging to achieve because the synthesis of cortisol is catalyzed by another enzyme that bears 93% sequence similarity with aldosterone synthase. Baxdrostat was shown to have 100:1 selectivity for enzyme inhibition, and baxdrostat, at several levels of dose, reduced plasma aldosterone levels but not cortisol levels in preclinical and phase 1 studies.
The multicenter, placebo-controlled trial was conducted for over 12 weeks. Two hundred forty-eight patients with treatment-resistant hypertension having BP of 130/80 mm Hg or higher and who received stable doses of at least three antihypertensive agents comprising a diuretic were randomly assigned with a once-daily dose of Baxdrostat (0.5 mg, 1 mg, or 2 mg) at varying amounts or a placebo. At the trial's entry, none of the patients had controlled blood pressure despite taking three or more medicines for high blood pressure.
The researchers assessed the changes in systolic blood pressure from baseline to week 12 (primary endpoint) in each baxdrostat group versus placebo.
The study led to the following findings:
- The researchers observed dose-dependent changes in systolic blood pressure of −17.5 mm Hg, −20.3 mm Hg,−12.1 mm Hg, and −9.4 mm Hg in the 1-mg, 2-mg, 0.5-mg, and placebo groups, respectively.
- The difference in systolic blood pressure change between the 2-mg group and the placebo group was −11.0 mm Hg, and the difference between the 1-mg group and the placebo group was −8.1 mm Hg.
- No deaths were seen during the trial, no serious adverse events were attributed to baxdrostat, and there were no instances of adrenocortical insufficiency.
- Baxdrostat-related increases in the potassium level of 6.0 mmol per litre or more significantly occurred in 2 patients, but these increases did not recur after withdrawal and reinitiation of the drug.
"The findings of this first-of-its-kind drug are exciting, although there is a need for more eating before drawing comparisons with any existing medications," Morris Brown, Queen Mary University of London, London, UK, said in a press release. "But Baxdrostat offers hope to many people who do not respond to commonly used hypertension treatment."
Reference:
Freeman MW, Halvorsen YD, Marshall W, Pater M, Isaacsohn J, Pearce C, Murphy B, Alp N, Srivastava A, Bhatt DL, Brown MJ; BrigHTN Investigators. Phase 2 Trial of Baxdrostat for Treatment-Resistant Hypertension. N Engl J Med. 2022 Nov 7. doi: 10.1056/NEJMoa2213169. Epub ahead of print. PMID: 36342143.
