Lorundrostat’s Safe and Effective Blood Pressure Control

An aldosterone inhibitor called lorundrostat took a step towards becoming the first new antihypertensive agent class in nearly 15 years after safely and effectively treating patients with uncontrolled blood pressure in a Phase II trial.

  • Mineralys Therapeutics’ lorundrostat is an aldosterone synthase inhibitor, which addresses hypertension produced by excess production of aldosterone.  

The Phase II Target-HTN dose selection trial randomized 200 participants with uncontrolled hypertension who were taking at least two antihypertensive medications.

An initial cohort of 163 patients with suppressed plasma renin (PRA ≤1.0 ng/mL/h) and elevated plasma aldosterone (≥1.0 ng/dL) were randomized to either take a placebo or five different lorundrostat regimens. After 8 weeks, lorundrostat-takers achieved notable reductions in office systolic blood pressure…

  • 12.5 mg once daily: −6.9 mm Hg 
  • 50 mg once daily: −13.2 mm Hg 
  • 100 mg once daily: −14.1 mm Hg
  • 12.5 mg twice daily: −10.1 mm Hg
  • 25 mg twice daily: −13.8 mm Hg
  • Placebo once daily: −4.1 mm 

A second cohort of 37 patients without suppressed plasma renin (≥1.0 ng/mL/h) were randomized in a 1:6 ratio to either take a placebo or 100 mg of lorundrostat once daily. After 8 weeks, lorundrostat-takers achieved office systolic blood pressure reductions of…

  • 11.4 mm Hg, similar to the blood pressure reductions seen in the suppressed PRA cohort when taking 100 mg daily

Further analysis revealed that lorundrostat was particularly effective among obese participants and those also taking a thiazide-type diuretic.

Three serious adverse events occurred, only one of which was deemed treatment related, while potassium levels didn’t increase as much as anticipated, and decreases in renal function were similar to other drugs that affect kidney blood flow.

The authors called for more research into lorundrostat, and they won’t have to wait long as Mineralys Therapeutics is currently running another Phase II trial, and there’s a Phase III trial being planned. The authors also expect to see future research into how lorundrostat or similar aldosterone inhibitors could treat heart failure and chronic kidney disease.

The Takeaway
Lorundrostat has a lot more to prove, but these trial results suggest that it could become a valuable option in physicians’ hypertension toolbox. And given how many patients are living with uncontrolled hypertension, there’s clearly still a need for new tools to bring BP under control.

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