Kardigan Announces Positive Phase 2 Data for Tonlamarsen in Patients with Uncontrolled Hypertension Presented as Late-Breaker at ACC.26 and Simultaneously Published in JACC

Key Takeaways

• Tonlamarsen cut plasma angiotensinogen up to 67% after five doses.
• Both single and multiple doses lowered systolic BP ~6.7 mmHg.
• Highest baseline SBP patients saw 8.9 mmHg reduction.
• Home BP surge reductions 28% with five‑dose regimen.
• Phase 2b trial for acute severe hypertension planned later this year.

Pulse Analysis

Uncontrolled hypertension remains a leading driver of cardiovascular morbidity, and acute severe hypertension (ASH) affects roughly six million U.S. emergency‑room visits annually, yet no therapy is approved for post‑hospitalization blood‑pressure control. Tonlamarsen, an antisense oligonucleotide that silences hepatic angiotensinogen, attacks the renin‑angiotensin‑aldosterone system at its source, a strategy that could bypass the tolerance and adherence challenges of daily oral agents.

The KARDINAL Phase 2 trial demonstrated that repeated 90 mg monthly injections lowered plasma angiotensinogen by 67% and produced an average 6.7 mmHg reduction in office systolic pressure, comparable to a single‑dose arm. Notably, patients entering the study with SBP above 150 mmHg achieved an 8.9 mmHg drop, and home‑monitoring data showed a 28% decline in high‑BP surges. Safety was on par with placebo, with minimal renal effects, bolstering confidence for a larger Phase 2b study focused on ASH patients who are at heightened risk of organ damage.

If the upcoming Phase 2b trial confirms efficacy, tonlamarsen could become the first disease‑modifying therapy for a market estimated at billions of dollars, given the prevalence of resistant hypertension and the costly hospitalizations linked to ASH. Kardigan’s broader pipeline—including cardiac myosin activator danicamtiv and soluble guanylate cyclase activator ataciguat—positions the company as a potential leader in precision cardiovascular therapeutics, attracting investor interest and paving the way for antisense technologies in cardiology.