What can you do if a patient with hypertension can't control their blood pressure with the best available drugs? Soon, it may be possible to layer in a therapy from Mineralys Therapeutics – with a new mechanism of action – to help regain control.
That is the conclusion of the Advance-HTN study reported at the American College of Cardiology (ACC) meeting, which found that adding Mineralys' aldosterone synthase inhibitor lorundrostat to the current treatment of uncontrolled hypertension significantly lowered 24-hour blood pressure.
It is thought that around 10% of the 1.3 billion people with hypertension around the world struggle to control their blood pressure using the current main classes of antihypertensive, namely diuretics, calcium channel blockers, and renin-angiotensin system-targeting drugs. That puts them at risk of serious consequences including heart attack, kidney damage, and stroke.
The pivotal study found that lorundrostat lowered 24-hour systolic blood pressure at week 12 by 15.4 mmHg, 7.9 mmHg more than placebo, at a once-daily dose of 50mg. Pushing the dose higher gave no additional treatment benefit but did worsen side effects, which included elevated levels of blood potassium – a side effect that can cause cardiac issues – although all the increases were modest.
"This result was achieved in expertly treated patients who were taking an optimal standardised antihypertensive regimen. In other words, they were patients with uncontrolled and truly treatment-resistant hypertension," said Cleveland Clinic cardiologist Luke Laffin, who presented the data at ACC.
"Additionally, this study's use of 24-hour ambulatory blood pressure monitoring strengthens findings from previous studies of lorundrostat that used office-based monitoring, as ambulatory monitoring is a better predictor of future cardiovascular and kidney risk," he added.
Mineralys now has data from two pivotal trials of lorundrostat, having earlier reported positive results with the drug in the Launch-HTN, which recruited patients in real-world settings rather than the group receiving specialist care in Advance-HTN. It revealed a 19.0 mmHg absolute and 11.7 mmHg placebo-adjusted reduction in blood pressure at week 12.
Prospects for people with uncontrolled hypertension are starting to look up, as various therapies are poised to join decades-old mineralocorticoid receptor blocker spironolactone as treatment options.
Last year, Idorsia Pharma claimed FDA approval for Tryvio (aprocitentan) as the first endothelin receptor antagonist for resistant hypertension, while AstraZeneca has another aldosterone synthase inhibitor, baxdrostat, in phase 3 testing for this indication. AZ acquired baxdrostat when it bought CinCor for $1.3 billion in 2023.
Mineralys' drug is considered to be the furthest along in development in the new class, with others in the pipeline including Damian Pharma's dexfadrostat and Boehringer Ingelheim's vicadrostat (BI 690517).
The company is also running the phase 2 Explore-CKD trial of lorundrostat in chronic kidney disease and is expecting topline data in the coming weeks and recently started another phase 2 trial called Explore-OSA in patients with moderate-to-severe obstructive sleep apnoea (OSA) and hypertension.
https://pharmaphorum.com/news/acc25-mineralys-uncontrolled-hypertension-drug-aces-trial
