Kardigan announced on Mar. 30 that its experimental blood pressure drug, tonlamarsen, achieved a significant reduction in a key biomarker but did not show a difference in blood pressure outcomes between dosing groups in its Phase 2 trial.
The company said the findings are enough to move forward with further testing, despite the split result. The trial's outcome is important because it may lead to new treatment options for patients with uncontrolled hypertension who do not respond well to existing therapies.
In the study, nearly 200 patients with uncontrolled hypertension already taking two to five other medications received either one or five doses of tonlamarsen. The main goal was to see if repeated dosing would control blood pressure better than a single dose by measuring angiotensinogen (AGT) levels and changes in office systolic blood pressure (oSBP). Tonlamarsen led to a mean reduction of AGT by 67% after five monthly doses compared to a 23% drop after just one dose. However, both dosing strategies resulted in similar reductions in oSBP over the course of the study.
Luke Laffin, principal investigator and co-director at Cleveland Clinic’s Center for Blood Pressure Disorders, said: “While continued dosing with tonlamarsen reduced angiotensinogen more than a one-time treatment, both treatment strategies reduced blood pressure to a similar extent.” Laffin called for more research on tonlamarsen especially for patients who have trouble sticking with daily medicines.
Kardigan reported that tonlamarsen was generally well tolerated and had safety results consistent with earlier studies. The company stated there were no meaningful signs of worsening kidney function or other major side effects such as hypotension or hyperkalemia.
Kardigan plans next to test tonlamarsen in patients with acute severe hypertension following hospitalization. A posthoc analysis suggested those most affected by high blood pressure might benefit most from this therapy. The company launched in January 2025 backed by $300 million and is led by several former MyoKardia executives.
