"A Bit of a Surprise": Kardigan's Tonlamarsen Shows No Blood Pressure Benefit from Repeat Dosing in Phase 2 Trial

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Kardigan's Phase 2 KARDINAL trial tested tonlamarsen in ~200 patients with uncontrolled hypertension on multiple therapies.

Five monthly doses reduced angiotensinogen (AGT) levels by 67% vs. 23% with single dose (p<0.0001), meeting one co-primary endpoint.124

No significant difference in office systolic blood pressure (oSBP) reduction (-6.7 mmHg in both arms at week 20, p=0.97), due to unexpected prolonged effect in single-dose arm.135

Results presented at ACC 2026; drug well-tolerated, supports Phase 2b in acute severe hypertension.12

Single-dose durability surprised investigators, as AGT suppression lasted longer than expected given 2-4 week half-life.25

Sources:

1. https://www.biospace.com/drug-development/kardigan-blood-pressure-drug-proves-hypothesis-despite-split-phase-2-readout

2. https://www.tctmd.com/news/kardinal-monthly-tonlamarasen-may-not-enhance-bp-lowering-resistant-hypertension

3. https://www.ainvest.com/news/kardigan-krfg-0-70-phase-2-blood-pressure-surprise-sparks-binary-catalyst-setup-2603/

4. https://www.kardigan.bio/wp-content/uploads/2026/03/KardiganTLA201DataPresentationatACCPressRelease.pdf

5. https://www.acc.org/About-ACC/Press-Releases/2026/03/28/18/33/Investigational-Drug-Delivers-Mixed-Results-for-Uncontrolled-Blood-Pressure