My name Luke Laffin and I’m a preventive cardiologist and cardiovascular clinical trialist at that Cleveland Clinic.
At the ACC 2026 Scientific Sessions, I presented the results of the CARDINAL trial, which was a study of the efficacy and safety of tonlamarsen in the treatment of uncontrolled hypertension.
Tonlamarsen is an investigational antisense oligonucleotide. So it’s a nucleic acid therapeutic that’s injected every 30 days and suppresses plasma angiotensinogen.
The research consisted of three parts, basically. The first was a placebo drug, and to get a placebo, you had to have a GFR above 30. You should already be taking two to five antihypertensive medications and your office systolic blood pressure should be between 135 and 170.
If after the introduction of placebo, after four weeks, as an injection of basically saline, then all patients were admitted, registered and received a dose of tonlamarsen. All received 90 milligrams.
And after four weeks, what we did was we randomized the participants to continued treatment with tonlamarsen every four weeks for the next 16 weeks or to placebo after that initial dose for the next 16 weeks.
Thus, the study examined two common endpoints. The first of these was the change in serum angiotensinogen from baseline percent change from before the initial injection of tonlamarsen to 20 weeks after.
And what we saw in the people who got continuous treatment with tonlamarsen was a 67% reduction in angiotensinogen at week 20.
What we saw in participants who were randomized to a single dose of tonlamarsen followed by placebo was somewhat unexpected. We did not see angiotensinogen return to baseline. They were suppressed by 23%, even 20 weeks after one injection.
And so, even though there was a significant difference between the treatment groups, we thought there would be more. There is a 44% treatment group difference.
A second co-primary endpoint was the change in baseline systolic blood pressure from before the first tonlamarsen injection to 20 weeks later.
And what we can see is that both groups had lower blood pressure from baseline. Both were less than seven millimeters of mercury to lower blood pressure.
And that raises the question, you know, is that blood pressure is more of a lagging biomarker after this initial profound angiotensinogen suppression, and we can see a reduction in blood pressure even as the angiotensinogen declines.
We are very excited to soon launch the Cardinal ASH, ASH training. And ASH means severe acute hypertension. So this includes participants who have recently been hospitalized with systolic blood pressure above 180 or diastolic blood pressure around 110, above 110, sorry. And we think, based on previous clinical evidence, that these patients are likely to benefit from tonlamarsen because they have an overactive renin angiotensin aldosterone system.
So if we can knock it down with a drug like tonlamarsen for a limited period of time, hopefully it will lower the angiotensinogen again, lower the blood pressure, but also reduce them coming back to the hospital or in the emergency department.
