Lorundrostat represents novel class of BP-lowering drugs

The investigational drug lorundrostat reduced 24-hour blood pressure (BP) at 12 weeks in patients with well-treated, uncontrolled hypertension in a phase 2b study. The safety profile was favourable in this hard-to-treat population.

The phase 2b Advance-HTN trial (NCT05769608) evaluated the safety and efficacy of the aldosterone synthase inhibitor lorundrostat in patients who had uncontrolled hypertension despite being treated with 2–5 BP-lowering drugs [1]. The 285 participants were put on a standard regimen of indapamide, olmesartan, and amlodipine and were randomised 1:1:1 to a placebo, 50 mg lorundrostat once daily, or to 50–100 mg lorundrostat once daily. “In the third arm, the dose could be escalated if BP was still uncontrolled and the patient did not display adverse events,” clarified Dr Luke Laffin (Cleveland Clinic, OH, USA). “About 40% of the participants were women, and over 50% of the participants were Black,” highlighted Dr Laffin. The primary outcome was the change in 24-hour average systolic BP at week 12.

At week 12, the primary endpoint was met, with reductions of 7.4, 15.4, and 13.9 mmHg in the placebo, 50 mg (95% CI -13.3 to -2.6; P=0.001), and 50–100 mg arms (95% CI -11.8 to -1.2; P=0.006), respectively. Moreover, the difference in BP reduction between placebo and lorundrostat was already significant after 4 weeks of therapy (-6.2 vs -11.5; 95% CI -8.4 to -2.3; P<0.001). The BP effect was achieved irrespective of race, sex, or weight. Hypotension (3% vs 8%), hyponatraemia (6% vs 9%), and hyperkalaemia >6.0 mmol/L (0% vs 5%) were more common in the 50 mg arm than in the placebo arm.

“Lorundrostat effectively lowered 24-hour BP among patients with well-treated, uncontrolled, and true resistant hypertension,” concluded Dr Laffin. “The dose-escalation strategy did not lead to larger reductions in BP than the stable 50 mg strategy, but was associated with a higher number of adverse events. Drugs that target aldosterone production, such as lorundrostat have great potential for reducing BP and cardiovascular risk,” stated Dr Laffin. “It is important that we test these new therapies in high-risk populations, who may have the largest benefit from them.” Lorundrostat is further explored in the phase 3 Launch-HTN trial (NCT06153693), results of which are expected soon.

1. Laffin LJ, et al. Advance-HTN: Lorundrostat efficacy and safety in patients with uncontrolled hypertension. Late-breaking Clinical Trials III, ACC 2025 Scientific Session, 29–31 March, Chicago, USA.

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Posted on 22 May 202521 May 2025