tonlamarsen (ION904) / Ionis, Kardigan - LARVOL DELTA

Blood Pressure Lowering Following a Single Dose of Tonlamarsen Compared with a Single Dose of Placebo: A Post-Hoc Analysis of the KARDINAL Randomized Trial (AHA 2026) - "Abstract is embargoed at this time."

Clinical • Retrospective data • Cardiovascular • Hypertension

Extended Follow-Up of the KARDINAL Trial Assessing the Effect of Tonlamarsen in Uncontrolled Hypertension (ESC 2026) - No abstract available

Late-breaking abstract • Cardiovascular • Hypertension

KARDINAL-ASH: Study of Efficacy and Safety of Tonlamarsen in Participants With a Recent Hospitalization and a Concurrent Episode of Acute Severe Hypertension (clinicaltrials.gov) - P2 | N=140 | Recruiting | Sponsor: Kardigan, Inc. | N=100 ➔ 140

Enrollment change • Cardiovascular • Hypertension

KARDINAL-ASH: Study of Efficacy and Safety of Tonlamarsen in Participants With Acute Severe Hypertension Recently Discharged From the Hospital (clinicaltrials.gov) - P2 | N=100 | Recruiting | Sponsor: Kardigan, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Cardiovascular • Hypertension

Efficacy of Tonlamarsen in Patients With Uncontrolled Hypertension: The KARDINAL Phase 2 Randomized Clinical Trial. (PubMed, J Am Coll Cardiol) - P2 | "Among individuals with uncontrolled hypertension, monthly tonlamarsen administration was more effective at lowering plasma angiotensinogen compared with a single tonlamarsen dose, but there was no additional BP reduction. (A Study to Investigate Tonlamarsen for the Treatment of Adults With Uncontrolled Hypertension [KARDINAL]; NCT06864104)."

Clinical • Journal • P2 data • Cardiovascular • Hypertension

KARDINAL-ASH: Study of Efficacy and Safety of Tonlamarsen in Participants With Acute Severe Hypertension Recently Discharged From the Hospital (clinicaltrials.gov) - P2 | N=100 | Not yet recruiting | Sponsor: Kardigan, Inc.

New P2 trial • Cardiovascular • Hypertension

A Study to Investigate Tonlamarsen for the Treatment of Adults With Uncontrolled Hypertension (KARDINAL) (clinicaltrials.gov) - P2 | N=206 | Completed | Sponsor: Kardigan, Inc. | Active, not recruiting ➔ Completed

Trial completion • Cardiovascular • Hypertension

Angiotensinogen Reconsidered: Evolving Perspectives in Hypertension Research. (PubMed, Hypertension) - "Recent translational advances, including RNA-based therapeutics such as small interfering RNAs (zilebesiran) and antisense oligonucleotides (tonlamarsen), demonstrate promising blood pressure reductions and favorable safety profiles in clinical trials. AGT also shows potential as a biomarker for hypertensive nephropathy and treatment responsiveness. This review underscores the value of AGT as an upstream therapeutic target and diagnostic marker, offering new avenues for precision medicine and long-acting strategies in the management of both conventional and resistant hypertension while possibly addressing medication adherence-related obstacles."

Journal • Review • Cardiovascular • Chronic Kidney Disease • Genetic Disorders • Hypertension • Inflammation • Nephrology • Obesity • Renal Disease

Kardinal: A Phase 2 Study Of Tonlamarsen For The Treatment Of Uncontrolled Hypertension (ACC 2026) - "Abstract is embargoed at this time."

Late-breaking abstract • P2 data • Cardiovascular • Hypertension

A Study to Investigate Tonlamarsen for the Treatment of Adults With Uncontrolled Hypertension (KARDINAL) (clinicaltrials.gov) - P2 | N=206 | Active, not recruiting | Sponsor: Kardigan, Inc. | N=700 ➔ 206 | Trial completion date: Dec 2027 ➔ Mar 2026 | Trial primary completion date: Feb 2027 ➔ Jan 2026

Enrollment change • Trial completion date • Trial primary completion date • Cardiovascular • Hypertension

A Study to Investigate Tonlamarsen for the Treatment of Adults With Uncontrolled Hypertension (clinicaltrials.gov) - P2 | N=700 | Active, not recruiting | Sponsor: Kardigan, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Cardiovascular • Hypertension

A Study to Investigate Tonlamarsen for the Treatment of Adults with Uncontrolled Hypertension (clinicaltrials.gov) - P2 | N=700 | Recruiting | Sponsor: Kardigan, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Cardiovascular • Hypertension

Effect of ION904, an Antisense Inhibitor of Angiotensinogen Production: Results of Phase 1 and Phase 2 Pilot Studies (AHA 2023) - "We previously published that inhibiting angiotensinogen (AGT) mRNA in hepatocytes with GalNAc-modified antisense oligonucleotide (ASO)-IONIS-AGT-LRx given subcutaneously (SC) weekly is effective in significantly reducing plasma angiotensinogen (AGT) with no on-target or off-target effects. Monthly administration of ION904 demonstrated significant plasma AGT reductions with a favorable safety and tolerability profile supporting development in heart failure and hypertension."

Clinical • P1 data • P2 data • Cardiovascular • Congestive Heart Failure • Heart Failure • Hematological Disorders • Hepatology • Hypertension • Hypotension • Liver Failure • Nephrology • Renal Disease • Thrombocytopenia

A Study to Assess the Safety, Tolerability, and Efficacy of Monthly Subcutaneous Administration of ION904 in Participants With Uncontrolled Hypertension (clinicaltrials.gov) - P2 | N=48 | Completed | Sponsor: Ionis Pharmaceuticals, Inc. | Active, not recruiting ➔ Completed

Trial completion • Cardiovascular • Hypertension

A Study to Assess the Safety, Tolerability, and Efficacy of Monthly Subcutaneous Administration of ION904 in Participants With Uncontrolled Hypertension (clinicaltrials.gov) - P2 | N=48 | Active, not recruiting | Sponsor: Ionis Pharmaceuticals, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Cardiovascular • Hypertension

A Study to Assess the Safety, Tolerability, and Efficacy of Monthly Subcutaneous Administration of ION904 in Participants With Uncontrolled Hypertension (clinicaltrials.gov) - P2 | N=48 | Recruiting | Sponsor: Ionis Pharmaceuticals, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Hypertension

A Study to Assess the Safety, Tolerability, and Efficacy of Monthly Subcutaneous Administration of ION904 in Participants With Uncontrolled Hypertension (clinicaltrials.gov) - P2 | N=48 | Not yet recruiting | Sponsor: Ionis Pharmaceuticals, Inc.

New P2 trial • Hypertension

A Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ION904 (clinicaltrials.gov) - P1 | N=40 | Completed | Sponsor: Ionis Pharmaceuticals, Inc. | Active, not recruiting ➔ Completed

Trial completion

A Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ION904 (clinicaltrials.gov) - P1; N=40; Active, not recruiting; Sponsor: Ionis Pharmaceuticals, Inc.; Recruiting ➔ Active, not recruiting; N=72 ➔ 40

Clinical • Enrollment change • Enrollment closed

A Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ION904 (clinicaltrials.gov) - P1; N=72; Recruiting; Sponsor: Ionis Pharmaceuticals, Inc.; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open