While tonlamarsen missed one of two co-primary endpoints, Kardigan says the drug has shown a clinically meaningful effect on blood pressure, supporting advancement into Phase 2b.
Kardigan’s blood pressure drug reduced a key biomarker and spurred “clinically meaningful” changes in blood pressure, the company said. But the Phase 2 trial did not show major differences in effects between treatment arms, leading to a split result for the mid-stage test.
Nevertheless, Kardigan, the new biotech that has become home for a handful of alumni from MyoKardia after its acquisition by Bristol Myers Squibb in 2020, has the evidence needed to advance the drug into a Phase 2b trial, according to a Saturday press release.
In the trial, tonlamarsen was tested in just under 200 patients with uncontrolled hypertension on a background of two to five therapies. Patients were split based on their baseline in-office systolic blood pressure (oSBP), with the single dose at 147.6 mmHg and the five-dose arm at 145.9 mmHg.
The goal of the study was to assess tonlamarsen’s ability to bring blood pressure under control, as measured via the biomarker angiotensinogen (AGT), with a co-primary endpoint looking for differences in oSBP between the two dose groups.
On the first measure, tonlamarsen achieved a 67% mean reduction in AGT levels after five monthly doses, compared to a 23% reduction after a single dose.
However, the second endpoint was unsuccessful, with no difference in oSBP between the dose arms from baseline to week 20. Kardigan blamed this on “an unexpected, prolonged reduction in blood pressure in the single-dose arm.”
“While continued dosing with tonlamarsen reduced angiotensinogen more than a one-time treatment, both treatment strategies reduced blood pressure to a similar extent,” said Luke Laffin, principal investigator and co-director of the Center for Blood Pressure Disorders in the Heart, Vascular & Thoracic Institute at Cleveland Clinic, in a statement provided by Kardigan. Laffin urged continued study of tonlamarsen, particularly in patients who struggle to take daily medicines.
The results support tonlamarsen’s advancement into a Phase 2b test of patients with acute severe hypertension (ASH) post-hospitalization, the company said. Kardigan conducted a posthoc analysis that showed patients with the highest hypertension burden had the greatest benefit, which supports advancement into this population.
Tonlamarsen was generally well tolerated, and the safety profile was comparable to previous studies, according to Kardigan. While the company did not provide specific safety data, it said that “worsening renal function was uncommon and there were no meaningful signs of treatment-related hypotension or hyperkalemia.”
Kardigan, a member of BioSpace’s NextGen Class of 2026, launched in January 2025 with a whopping $300 million and a goal to tackle cardiovascular disease at the root cause. The biotech’s initial focus is on disease opportunities and patient populations that are resistant or poorly managed on current therapies, including primary and secondary cardiomyopathies leading to heart failure.
Much of the company’s leadership comes from MyoKardia, the developer or mavacamten, which was sold to BMS for $13.1 billion in October 2020. The drug was later approved in 2022 as Camzyos to treat symptomatic obstructive hypertrophic cardiomyopathy (oHCM).
