New drug shows promise for hard-to-treat high blood pressure

Key Takeaways

• New hope for hypertension: UC San Diego researchers found that lorundrostat significantly lowers systolic blood pressure in patients with treatment-resistant hypertension.

• Promising clinical results: Participants taking lorundrostat experienced a 15-point drop in systolic blood pressure, compared to 7 points with placebo, according to a Phase II trial.

• Next steps: Encouraged by these findings, researchers are planning a larger Phase III trial to further investigate lorundrostat's safety and effectiveness.

A new investigational drug called lorundrostat could represent a breakthrough for patients struggling with treatment-resistant hypertension, also known as high blood pressure.

Researchers at the University of California San Diego School of Medicine conducted a nationwide clinical trial, publishing the results this week in the New England Journal of Medicine. The study suggests that the drug significantly lowers systolic blood pressure in patients for whom standard medications have failed.

“This study was designed to look at the impact of a novel medication in lowering blood pressure for individuals whose hypertension is inadequately controlled by current standard medications,” Dr. Michael Wilkinson, principal investigator at UC San Diego School of Medicine, said in a statement accompanying the release of the results, 

In the Phase II clinical trial, which included 285 participants across the country, patients who received lorundrostat saw their systolic blood pressure — the top number in a blood pressure reading — drop by an average of 15 millimeters of mercury (mmHg). In contrast, those who received a placebo experienced a 7-point reduction. Systolic blood pressure is a critical measure because high readings increase the risk of heart disease, the leading cause of death in the United States.

The trial, conducted in collaboration with the Cleveland Clinic Coordinating Center for Clinical Research, required all participants to initially follow a standardized regimen of antihypertensive medication for three weeks. Afterward, 190 participants were assigned lorundrostat, while 95 received a placebo. Blood pressure was monitored continuously over a 12-week period.

A novel pathway for treatment

Researchers targeted aldosterone — a hormone that regulates blood pressure but can contribute to hypertension when imbalanced — as a novel pathway for treatment. Lorundrostat works by halting the production of aldosterone, offering a new strategy for managing difficult-to-treat high blood pressure.

“While blood pressure readings remained elevated at the end of this Phase II trial in some participants treated with lorundrostat, we find these results promising because almost all participants involved in the study were not able to sufficiently lower their blood pressure with medication before,” Wilkinson explained.

Importantly, the trial featured a diverse patient group, potentially paving the way for a treatment that benefits a broader population of people at risk for heart disease. Given the positive outcomes, researchers are preparing to launch a larger Phase III trial to further assess lorundrostat's safety and effectiveness.