Uncontrolled hypertension remains a significant public health challenge, affecting millions of adults worldwide and increasing the risk of heart disease, stroke, and kidney failure. A recent publication, “Efficacy of Tonlamarsen in Patients with Uncontrolled Hypertension: The KARDINAL Phase 2 Randomized Clinical Trial,” provides important insight into a novel approach to managing this condition. DelRicht Research investigator Dr. Patrick Dennis at Touro Medical Center in New Orleans, LA, served as a principal investigator and contributing author on this pivotal study.

About the Study

This Phase 2 randomized, placebo-controlled trial evaluated the safety and efficacy of monthly 90 mg tonlamarsen, an investigational antisense oligonucleotide targeting hepatic angiotensinogen synthesis, in adults with uncontrolled hypertension on multiple antihypertensive medications. Participants underwent a three-part treatment period: a 4-week placebo lead-in, a 4-week active run-in with a single dose of tonlamarsen, and subsequent randomization to receive either monthly tonlamarsen or matching placebo for 16 weeks. Co-primary endpoints assessed changes from baseline to Week 20 in plasma angiotensinogen levels and office systolic blood pressure, providing a comprehensive view of both mechanistic and clinical outcomes.

Key Findings

The study demonstrated that monthly tonlamarsen administration significantly reduced plasma angiotensinogen levels compared to a single dose, with least squares mean percent changes of -67.2% versus -23.0%, respectively. This mechanistic effect highlights the potential of tonlamarsen to target a key upstream step in the renin–angiotensin–aldosterone system. Despite this robust reduction, no additional lowering of office systolic blood pressure was observed beyond what was achieved with a single dose. Importantly, serious adverse events were infrequent and occurred at similar rates across treatment groups, supporting a favorable safety profile for monthly administration.

Dr. Dennis’s Impact

With extensive experience in cardiovascular research and a history of high-performing clinical trial oversight, Dr. Patrick Dennis exemplifies the role of skilled investigators in advancing novel therapies. His contributions as principal investigator and co-author of the KARDINAL study reflect a commitment to rigorous trial execution, meticulous patient care, and generating meaningful data to inform future therapeutic strategies.

Collaborative Efforts and Leadership

We also recognize Tassos Gianakakos and the Kardigan team for their leadership in developing innovative approaches targeting the renin-angiotensin-aldosterone system. Their commitment to advancing antisense therapies for hypertension, alongside dedicated site teams and investigators, ensures that promising treatments are evaluated with high scientific rigor and patient safety at the forefront.

Explore the Full Publication

Read the full publication, “Efficacy of Tonlamarsen in Patients with Uncontrolled Hypertension: The KARDINAL Phase 2 Randomized Clinical Trial,” to learn more about this important advancement in hypertension management.

At DelRicht Research, we are proud to support investigators like Dr. Dennis who are helping move cardiovascular science forward. Through collaboration, innovation, and patient-centered research, we remain committed to generating data that improves outcomes for individuals with complex, treatment-resistant conditions and strengthens evidence-based care for the broader healthcare community.