A groundbreaking treatment for individuals grappling with arduous-to-control high blood pressure has demonstrated remarkable efficacy in a important global clinical trial. The Phase 3 Launch-HTN study revealed that lorundrostat, an aldosterone synthase inhibitor, effectively and safely reduced blood pressure across a diverse patient population that had previously shown resistance to other medications. This marks a pivotal advancement in the development of the first targeted aldosterone synthase inhibitor for such conditions.

Understanding Hypertension and Aldosterone’s Role

Hypertension, commonly known as high blood pressure, occurs when the force of blood against artery walls consistently exceeds normal levels. Globally, it affects one in three adults, according to the World Health Organization, substantially increasing the risk of heart disease, heart attacks, and strokes. resistant hypertension, a especially challenging form, remains elevated despite a person adhering to three different blood pressure medications at their maximum recommended doses.

Lorundrostat: A Novel Approach

The Launch-HTN trial, presented at the 34th European Meeting on Hypertension and Cardiovascular Protection, showcased lorundrostat as a safe and effective treatment for individuals with uncontrolled or resistant hypertension. lorundrostat functions by specifically targeting and inhibiting CYP11B2, the enzyme responsible for aldosterone production, thereby lowering aldosterone levels. The study demonstrated consistent blood pressure reductions across a large and diverse patient group, representing the largest Phase 3 trial to date for this treatment class.

Expert Insights on lorundrostat

Dr. Manish Saxena, clinical co-director of the William Harvey Heart Center at Queen Mary university of London and hypertension specialist from Barts Health NHS Trust, served as the study’s lead investigator. He emphasized the significant unmet need in hypertension management:

Despite available treatments, more than 40% of adults with hypertension worldwide are not reaching their blood pressure goal. Aldosterone pathway plays crucial role in blood pressure regulation,and leads to blood pressure related complications such as heart failure and kidney problems.in the Launch-HTN trial we explored the safety and effectiveness of lorundostat, which belongs to a new class of drugs called aldosterone synthase inhibitors that block production of hormone aldosterone from the adrenal glands.
Manish Saxena, MD

Dr.Saxena further noted that the Launch-HTN trial is the largest Phase 3 hypertension study with a novel drug, demonstrating a good safety profile and consistent blood pressure reduction across diverse patient groups.

The Launch-HTN trial is the largest phase 3 hypertension study with a novel drug. We tested lorundostat in a large, diverse patient population recruited globally and found that it has good safety profile and lowered blood pressure consistently in all of our patient groups.
Manish Saxena, MD

He also explained the mechanism of action:

Hormone aldosterone secreted from adrenal glands in the body plays an important role in driving blood pressure. now there is more awareness of dysregulated aldosterone secretion in patients with difficult to treat blood pressure. Lorundrostat blocks biosynthesis of hormone aldosterone in the body and helps reduce blood pressure.
Manish Saxena, MD

Trial Details and Results

The Launch-HTN trial was a global, randomized, double-blind, and placebo-controlled study involving adult participants whose blood pressure remained uncontrolled despite taking two to five antihypertensive medications. The trial, designed to mirror real-world clinical practice, utilized automated office blood pressure (AOBP) measurements and allowed participants to continue their existing treatments. Lorundrostat, administered once daily at a 50 mg dose, demonstrated significant and sustained reductions in systolic blood pressure, dropping by 16.9 mmHg at Week 6 (a 9.1 mmHg reduction compared to placebo) and by 19 mmHg at Week 12 (an 11.7 mmHg reduction versus placebo).

the LAUNCH-HTN trial demonstrated blood pressure lowering efficacy and safety of lorundrostat in a vrey diverse patient group with uncontrolled and difficult to treat hypertension that were on background 2-5 blood pressure lowering medication. The blood pressure reduction observed was consistent across key sub-groups, significant and clinically meaningful.
Manish Saxena, MD

Additional Expert Perspectives

Dr.Cheng-Han Chen, a board-certified interventional cardiologist and medical director of the Structural Heart Program at MemorialCare Saddleback Medical Centre, highlighted the meaning of this new drug class:

Aldosterone synthase inhibitors are a new class of drugs being studied for the treatment of hypertension. This trial found that lorundrostat, one of these new types of drugs, was safe and effective for patients with uncontrolled or resistant hypertension. This puts us one step closer to having another tool in our arsenal for patients with difficult to control blood pressure despite being on multiple medications.
cheng-Han Chen, MD

He also emphasized the potential impact on patient outcomes:

Many patients have high blood pressure that are not under control with multiple classes of medications. By having another class of blood pressure medications at our disposal, we will better be able to reduce rates of hypertension in our population and improve health outcomes.
Cheng-Han Chen, MD

Dr. Rigved Tadwalkar, a consultative cardiologist and director of Digital Conversion at Pacific Heart Institute, echoed this sentiment:

This is a meaningful step forward. We still see far too many patients with uncontrolled or resistant hypertension,even when they’re on three,four,sometimes five medications. The reality is that for a significant subset of these patients, aldosterone is driving the problem and until now, we haven’t had a way to target that mechanism directly in a safe, practical way.
Rigved Tadwalkar, MD, FACC

Dr.Tadwalkar further elaborated on the drug’s potential impact:

Lorundrostat appears to change that. It inhibits aldosterone synthesis at the enzymatic level, and based on this trial, it does so with a good safety profile and consistent efficacy across a diverse population. The blood pressure reductions- nearly 17 mmHg at 6 weeks and close to 19 mmHg at 12- are significant, especially when you consider that these were already heavily treated patients. That kind of additional drop is not something we usually see at this stage of therapy.
Rigved tadwalkar, MD, FACC

He also noted the clinical relevance of the trial design:

Since patients stayed on their background medications, these results feel more clinically relevant than more tightly controlled washout studies. It’s a welcome addition to the field, even as we continue to see the limitations of existing therapies, including newer device-based approaches like renal denervation.
Rigved Tadwalkar, MD, FACC

Dr. Tadwalkar concluded by highlighting the potential for lorundrostat to improve patient lives and address the broader public health challenge of uncontrolled hypertension:

if lorundrostat becomes widely available,it could offer a new option for patients who’ve exhausted standard pathways. For people living with resistant hypertension, many of whom are already dealing with co-morbidities like kidney disease or heart failure, having another tool, especially one that targets the underlying hormonal dysregulation, could make a real difference in long-term outcomes.
Rigved Tadwalkar, MD, FACC

He also emphasized the broader implications for public health:

At the population level, we’re still facing a huge burden from poorly controlled blood pressure. A drug like this,if used properly,could help narrow that treatment gap. it’s certainly not a silver bullet, but it’s a step toward more personalized, mechanism-specific care. This is something the hypertension field has needed for a long time.
Rigved Tadwalkar, MD, FACC