Tonlamarsen Shows Sustained Blood Pressure Reduction After Treatment Withdrawal: Study

A new study published in the Journal of American College of Cardiology showed that in people with uncontrolled hypertension, giving tonlamarsen monthly was more successful in reducing plasma angiotensinogen levels than a single dose of tonlamarsen, although it did not lead to further reduction in blood pressure.

Tonlamarsen is a new type of treatment that targets the creation of angiotensinogen in the liver using antisense oligonucleotide technology. The effectiveness and safety of this treatment in individuals with high blood pressure have not been determined. This research evaluated how safe and effective a 90 mg dose of tonlamarsen given as a subcutaneous injection once a month for 5 months is when compared to a single dose of tonlamarsen followed by a placebo.

In this study, adults with high office systolic blood pressure (>135 mm Hg) who were taking 2 to 5 antihypertensive medications were randomly assigned to receive either the study drug or a placebo. The trial consisted of three parts: a 4-week period with a placebo, followed by a 4-week period with a single dose of tonlamarsen, and then randomization to receive 4 more doses of tonlamarsen or a placebo over 16 weeks.

The main goals of the study were to compare the differences between the groups in the changes in plasma angiotensinogen levels and office systolic blood pressure from the start to week 20. During the initial stage, 279 individuals were given a dummy treatment, while 206 were administered 90 mg of tonlamarsen during the active phase, and 198 were chosen at random.

The average blood pressure dropped from 147/89 mmHg after the placebo to 140/87 mmHg after taking tonlamarsen. By the 20th week, there was a 23.0% reduction in plasma AGT with a single dose of tonlamarsen followed by a placebo and a 67.2% decrease with monthly doses.

This resulted in a difference of -44.1% between the groups, but, the decrease in office systolic blood pressure was the same in both groups at -6.7 mmHg, showing no significant difference between them (-0.1 mmHg; P = 0.97). Severe adverse events were infrequent and similar across all treatment categories.

Overall, over a period of 5 months, a monthly intake of 90-mg tonlamarsen resulted in a more significant reduction of plasma AGT compared to a one-time dose followed by a placebo in individuals with uncontrolled high blood pressure. 

Source: 

Laffin, L. J., Wang, Q., Sarraju, A., Touyz, R. M., Schlaich, M. P., Cohen, D. L., Mahfoud, F., Mitchell, L. M., Mitchell, J., Wolski, K., Dennis, P., Akere, A., Li, W., Chen, G., Cohen, Y. Z., Kim, J., Cooper, C. G., Ramesan, P., Edelberg, J. M., … KARDINAL Investigators. (2026). Efficacy of tonlamarsen in patients with uncontrolled hypertension: The KARDINAL phase 2 randomized clinical trial. Journal of the American College of Cardiology, 87(18), 2508–2520. https://doi.org/10.1016/j.jacc.2026.03.034