Idorsia’s aprocitentan improved key prognostic indicators in patients with difficult-to-control hypertension

New analysis from landmark Phase 3 PRECISION trial published in the Journal of Hypertension highlights aprocitentan led to improvements in dipping pattern and BP load

Findings reinforce the role of aprocitentan’s novel endothelin pathway mechanism in addressing significant medical need in difficult-to-control hypertension

Allschwil, Switzerland – November 10, 2025
Idorsia Ltd (SIX: IDIA) announced the publication of a new analysis from the landmark Phase 3 PRECISION study in the Journal of Hypertension titled “Effects of aprocitentan on prognostically relevant ambulatory blood pressure-derived variables in resistant hypertension”1. The analysis examined the changes in variables derived from ambulatory BP monitoring that are shown to drive better outcomes for patients at high risk of cardiovascular events.

Aprocitentan (TRYVIO™/JERAYGO™), the first approved antihypertensive targeting the endothelin pathway, substantially lowered 24-hour blood pressure (BP) in patients with confirmed resistant hypertension, with particularly pronounced effects at night. Night-time BP is a strong indicator of poor long-term outcome. The new analysis shows that aprocitentan on top of at least triple anti-hypertensive therapy improved multiple characteristics of resistant hypertension that are linked to poor clinical outcomes, including reducing blood pressure load and normalizing night-time “dipping” patterns, and is efficacious in patients with increased arterial stiffness and salt sensitivity.

Markus Schlaich, MD, FAHA, FESC, ISHF, The University of Western Australia / Royal Perth Hospital and an investigator in the PRECISION study commented:
“Aprocitentan resulted in substantial and sustained improvements in ambulatory BP parameters which are predictive of cardiovascular risk. As a result, aprocitentan is positioned as a promising option that could reduce cardiovascular events and improve long-term outcomes in patients with resistant hypertension.”

Michael A. Weber, MD, preventative cardiologist and hypertension specialist at Downstate College of Medicine of the State University of New York, commented:
“The availability of aprocitentan in routine clinical practice is a welcome and much needed addition to our armamentarium to effectively treat a broad range of patients with difficult-to-control hypertension. It has the added benefit of targeting the otherwise unopposed yet highly relevant endothelin mechanism in the pathogenesis of hypertension, potentially yielding therapeutic effects beyond BP lowering per se.”

John M. Flack, MD, MPH, Director, Hypertension Center, Southern Illinois University School of Medicine, commented:
“This is an important analysis as it provides insight into the benefit of targeting the endothelin system with aprocitentan to address the needs of the many patients with difficult-to-control hypertension, without risks of hyperkalemia, known drug interactions or worsening renal function. This makes aprocitentan a unique and important treatment option for physicians who are struggling to maintain 24-hour blood pressure control in their patients, particularly at night.”

There are 1.4 billion people worldwide living with hypertension.2 Hypertension remains a leading global health challenge and the number one modifiable risk factor for early morbidity and mortality. Despite advances in treatment, many patients still struggle with uncontrolled blood pressure, leaving them at significantly higher risk of heart attack, stroke, kidney failure, and premature death.3 In the US, approximately 50% of patients living with hypertension on multiple treatments do not have their blood pressure under control.4 Consistent 24-hour blood pressure control is an important clinical outcome in patients with difficult-to-control hypertension.5-7 Multiple studies have demonstrated that 24-hour blood pressure is a more powerful predictor of cardiovascular events than a clinic-based measurement.8-10

Endothelin-1 (ET-1) is a potent vasoconstrictor that also induces neurohormonal activation, vascular hypertrophy and remodeling, cardiac hypertrophy and fibrosis, and endothelial dysfunction. In hypertension, both ETA and ETB receptors mediate harmful effects of ET-1.11 As a vasoconstrictor, co-mitogenic agent, linking pulse pressure and vascular remodeling, and mediator of aldosterone and catecholamine release, endothelin is a key player in hypertension and end-organ damage.12,13

About the analysis1
The Phase 3 PRECISION study demonstrated both the safety and the efficacy of aprocitentan to lower office BP in patients with resistant hypertension. The post-hoc analysis evaluated the BP-lowering effects of aprocitentan on derivatives of ambulatory BP measurements (ABPM) – dipping pattern, BP load, heart rate, arterial stiffness, and salt sensitivity.

The analysis revealed that in addition to significant and sustained daytime and nighttime ambulatory BP reduction, aprocitentan was associated with:

In patients classified as non-dippers – those who do not have the normal nighttime BP drop – aprocitentan treatment resulted in a higher proportion achieving normalization of their dipping pattern compared to placebo. This normalization of the nocturnal BP fall is a positive prognostic indicator with a lower risk of cardiovascular disease.Aprocitentan significantly reduced the BP load – the proportion of time BP exceeds threshold values – by about 20% during both daytime and nighttime, potentially lowering the risk of hypertension-mediated organ damage.Despite the BP lowering effect of aprocitentan, heart rate remained unchanged at Week 36.The blood pressure lowering effect of aprocitentan was consistently observed regardless of the patients’ baseline arterial stiffness or salt sensitivity, indicating aprocitentan’s effectiveness even in patients with clinical features traditionally associated with poor BP control.

About aprocitentan
Aprocitentan is Idorsia’s once-daily, orally active, dual endothelin receptor antagonist, which inhibits the binding of ET-1 to ETA and ETB receptors. Aprocitentan is approved as TRYVIO® in the US for the treatment of systemic hypertension in combination with other antihypertensives and has been commercially available since October 2024. For more information see the Full Prescribing Information including BOXED Warning (PI and Medication Guide). TRYVIO is now included in the American College of Cardiology’s (ACC) and the American Heart Association’s (AHA) new comprehensive clinical practice guidelines for the management of high blood pressure. Aprocitentan is approved as JERAYGO® for the treatment of resistant hypertension in combination with other antihypertensives in the European Union, the UK, and Switzerland, and a marketing authorization application is under review in Canada.

About PRECISION14,15(NCT03541174)
PRECISION was a multicenter, blinded, randomized, parallel-group, Phase 3 study, which was performed in hospitals or research centers in Europe, North America, Asia, and Australia. Patients were eligible for randomization if their sitting systolic blood pressure was 140 mm Hg or higher despite taking standardized background therapy consisting of three antihypertensive drugs, including a diuretic. The study consisted of three sequential parts: Part 1 was the 4-week double-blind, randomized, and placebo-controlled part, in which 730 patients were randomized to aprocitentan 12.5 mg (n=243), aprocitentan 25 mg (n=243), or placebo (n=244) in a 1:1:1 ratio; Part 2 was a 32-week single (patient)-blind part, in which all patients received aprocitentan 25 mg (n=704); and Part 3 was a 12-week double-blind, randomized, and placebo-controlled withdrawal part, in which patients were re-randomized to aprocitentan 25 mg (n=307) or placebo (n=307) in a 1:1 ratio. The primary and key secondary endpoints were changes in unattended office systolic blood pressure from baseline to week 4 and from withdrawal baseline to week 40, respectively. Secondary endpoints included 24-h ambulatory blood pressure changes.

At baseline, 69.2% of patients were obese or severely obese, 54.1% had diabetes, 22.2% had stage 3-4 chronic kidney disease and 19.6% had congestive heart failure. 63% of randomized patients were receiving at least 4 anti-hypertensive therapies at screening.

Key PRECISION findings15
The least square mean change in office SBP at 4 weeks was –15.3 mmHg for aprocitentan 12.5 mg, –15.2 mmHg for 25 mg, and –11.5 mmHg for placebo, for a difference versus placebo of –3.8 mmHg (p=0.0042) and –3.7 mmHg (p=0.0046), respectively. Office diastolic blood pressure (DBP) also decreased with both aprocitentan doses compared to placebo (–3.9 mmHg for the 12.5 mg dose and –4.5 mmHg for the 25 mg dose). Office SBP and DBP were maintained during Part 2 in patients previously receiving aprocitentan and decreased within the first 2 weeks of Part 2 before stabilizing in those previously receiving placebo. In Part 3, office SBP after 4 weeks of withdrawal (the key secondary endpoint) increased significantly with placebo compared to aprocitentan (5.8 mmHg; p