The investigational drug tonlamarsen caused a significant and sustained reduction in angiotensinogen levels, but its effect on blood pressure was less clear, according to results presented at the American College of Cardiology's Annual Scientific Session (ACC.26) on Mar. 28.
High blood pressure remains a major health issue in the United States, with about half of adults having uncontrolled hypertension. New therapies like tonlamarsen are being developed for patients whose blood pressure is not managed by current medications.
Tonlamarsen is given as a monthly injection and works by suppressing angiotensinogen, which plays a role in regulating blood pressure. In a Phase 2 trial involving 206 patients across 39 U.S. sites, participants had an average systolic blood pressure of 147 mmHg despite taking two to five other medications. The study included both men and women, with about half identifying as Black or African American.
All participants received an initial dose of tonlamarsen before being split into two groups: one continued receiving the drug while the other switched to placebo injections for four months. At week 20, those who stayed on tonlamarsen saw their angiotensinogen levels drop by over two-thirds compared to baseline—a significant difference from those who switched to placebo. However, reductions in systolic blood pressure were similar between both groups after the first dose and remained steady through week 20.
Researchers said these mixed results might be due to the lasting effects of the initial dose given to all participants or other factors that are not yet fully understood. "One possibility, which we think is most likely, is that tonlamarsen lowers blood pressure by about 6-7 mmHg, and this is maintained even as angiotensinogen levels rise," said Laffin. "Another possibility is that residual angiotensin suppression among placebo participants resulted in greater blood pressure reduction than expected. It's also possible that decreasing angiotensin with tonlamarsen doesn't reduce blood pressure, although we think that's probably not likely based on the fact that blood pressure dropped during the drug run-in period." Participants continuing on tonlamarsen experienced more injection-site reactions compared to those switching to placebo.
Laffin also said that further research will be needed because this study did not measure cardiovascular outcomes and involved a relatively small number of patients. Researchers plan another study focusing on short-term use of tonlamarsen for acute severe hypertension.
