Lorundrostat lowers blood pressure compared with placebo at 12 weeks, suggests research
Among patients with uncontrolled hypertension, the investigational drug lorundrostat brought a significant reduction in blood pressure at 12 weeks compared with placebo, according to a study presented at the American College of Cardiology’s Annual Scientific Session (ACC.25).
The Phase 2b trial is only the second study to test lorundrostat’s blood pressure lowering ability in patients. Twenty-four-hour average ambulatory blood pressure, the trial’s primary endpoint, dropped by 7.9 mm Hg and 6.5 mm Hg more than placebo in the two study groups that received the drug (with one group receiving 50 mg of the drug daily and the other group receiving 50 mg to 100 mg). At four weeks, 42% of those taking lorundrostat had their blood pressure under control, compared with 19% in the placebo group.
“Lorundrostat effectively lowered blood pressure with an acceptable side effect profile,” said Luke Laffin, MD, a cardiologist at Cleveland Clinic and the study’s first author. “More studies are needed; however, this drug could be another tool in our armamentarium to reduce blood pressure and, ultimately, reduce the risk from uncontrolled hypertension in terms of outcomes like strokes, heart attacks and heart failure.”
High blood pressure, or hypertension, is a key modifiable risk factor for heart disease. Studies suggest that blood pressure remains uncontrolled in over two-thirds of people with hypertension in the United States, either because they are not taking blood pressure-lowering drugs or available drugs are not working for them.
Lorundrostat is in a new class of blood pressure medications called aldosterone synthase inhibitors (ASIs). Several ASIs are currently in development and are designed to work by disrupting the production of aldosterone, a hormone that can contribute to hypertension. Many existing blood pressure-lowering drugs work by blocking aldosterone from binding to its receptor but do not interfere with the hormone’s production.
The trial, called ADVANCE-HTN, enrolled 285 patients at 103 sites in the U.S. Participants had elevated blood pressure despite taking two to five blood pressure-lowering medications before joining the study. The average age of participants was 60 years and 40% were women. Over half of the study’s participants (53%) were Black.
“Black Americans have a disproportionate burden of treatment-resistant hypertension, yet they have been underrepresented in anti-hypertensive drug trials,” Laffin said. “It was very important to us to study this drug in this population that really needs new options for controlling blood pressure.”
The researchers said the results did not show any differences in the drug’s effectiveness among different racial groups.
The study began with a three-week run-in period during which all participants received a standardized set of blood pressure-lowering medications. Those who still had uncontrolled blood pressure at that point were then randomly divided into three groups and assigned to take either a placebo, 50 mg lorundrostat daily or 50 mg lorundrostat with the potential to increase to 100 mg daily if their blood pressure remained uncontrolled after four weeks. Among participants in the third group, 20% met the criteria to increase their dose to 100 mg and the rest continued taking 50 mg per day.
At four and 12 weeks, participants were asked to wear a device that continuously monitors blood pressure for 24 hours while going about their daily activities. On average, the 24-hour mean ambulatory blood pressure dropped in all three groups. At 12 weeks, this measurement fell by 15.4 mm Hg among those receiving 50 mg lorundrostat, 13.9 mm Hg among those receiving 50-100 mg lorundrostat and 7.4 mm Hg among those receiving a placebo. The change in blood pressure compared with placebo was significant in both lorundrostat groups, meeting the trial’s primary endpoint.
The results showed consistent patterns across secondary endpoints including change in blood pressure as measured in a medical office and in all types of blood pressure measurements at both four and 12 weeks.
The side effects experienced by patients taking lorundrostat were consistent with other drugs that work through a similar mechanism, researchers said. Some participants saw an increase in potassium in the blood and some experienced a decrease in glomerular filtration rate, a measure of kidney functioning.
“It was overall a well-tolerated drug,” Laffin said.
Another pivotal lorundrostat trial is currently underway with results expected later this year.
Reference:
Lorundrostat lowers blood pressure compared with placebo at 12 weeks, American College of Cardiology, Meeting: American College of Cardiology's Annual Scientific Session
