Efficacy of aprocitentan in patients across the cardiometabolic disease spectrum including obesity to be presented at AHA Hypertension

Two oral presentations at AHA Hypertension 2026 will highlight the substantial antihypertensive efficacy of aprocitentan in two hypertension populations from the PRECISION study: patients with obesity and patients across the cardiovascular-kidney-metabolic (CKM) continuum.

The analyses extend the clinical evidence supporting aprocitentan in these patients and further underscore the importance of blockade of the upregulated endothelin system as a therapeutic target in difficult-to-control hypertension, including true resistant hypertension.

Allschwil, Switzerland – October 5, 2026
Idorsia Ltd (SIX: IDIA) announces positive findings from two new analyses of the pivotal Phase 3 PRECISION study highlighting the importance of endothelin pathway blockade in patients with obesity-associated resistant hypertension and across the cardiovascular-kidney-metabolic continuum. The findings will be presented in oral sessions at the American Heart Association Hypertension Scientific Sessions 2026, taking place in Arlington, Virginia, from October 7 to 11, 2026.

Targeting the upregulated endothelin pathway in patients with obesity and hypertension
Obesity and hypertension are closely interconnected. Hypertension is one of the most common comorbidities of obesity and is a major contributor to cardiovascular and kidney damage in this population. As the prevalence of obesity continues to rise, the number of people living with obesity-associated hypertension is also expected to increase.¹

The obese population is more likely to develop hypertension that remains uncontrolled despite treatment with multiple antihypertensive medicines. The upregulation of the endothelin pathway appears to be an important system that had not been targeted in hypertension before aprocitentan. Adipose tissue releases endothelin-1, with greater release observed in obese people.¹ Obesity is therefore associated with increased detrimental effects of endothelin-1.^1-2
A new analysis of PRECISION evaluated aprocitentan in patients with resistant hypertension and obesity or severe obesity, many of whom were also living with diabetes, chronic kidney disease or albuminuria. The positive findings strengthen the evidence supporting endothelin pathway blockade in this population and provide new insights into the role of endothelin in obesity-associated resistant hypertension.

The results will be presented for the first time in an oral presentation by Dr. Michael A. Weber, MD:
Endothelin is a driver of hypertension in individuals with obesity: A post hoc analysis of the PRECISION study.
Markus Schlaich, Martine Clozel, Ruth Collins, Parisa Danaietash, John M. Flack, Johann Laurent, Krzysztof Narkiewicz, Ji-Guang Wang, and Michael A. Weber.
Saturday, October 10, 5:15 PM | Abstract Session 19 | Number 83

Targeting the upregulated endothelin pathway in patients with CKM and hypertension
Cardiovascular-kidney-metabolic (CKM) syndrome is defined as a health disorder attributable to the interconnections among obesity, diabetes, chronic kidney disease, and cardiovascular disease.^3,4 The risk of cardiovascular death nearly triples as CKM progresses from stages 0-1 to stage 4, while more than 64% of the US adult population is classified as CKM stages 2 to 4.³ Hypertension is a central driver across this continuum, contributing to chronic kidney disease progression, while dysfunction in the cardiovascular, kidney, and metabolic systems creates a self-reinforcing cycle that increases the risk of cardiovascular events, kidney failure, hospitalization and premature death.^3-5
Endothelin has detrimental consequences relevant to multiple components of CKM syndrome, including blood pressure regulation, kidney function and metabolic effects such as aldosterone production. This provides a strong rationale for examining endothelin inhibition across different stages of CKM syndrome.

A new analysis of PRECISION evaluated aprocitentan across early and advanced CKM stages. The positive findings further characterize the effects of endothelin pathway blockade across the CKM continuum and provide new insights into blood pressure control and other measures relevant to cardiovascular, kidney and metabolic health.

The findings will be presented for the first time in an oral session at the congress by Dr. John M. Flack, MD:
Endothelin as a therapeutic target across the cardiovascular-kidney-metabolic continuum: A post hoc analysis of the PRECISION study
Markus Schlaich, Martine Clozel, Parisa Danaietash, Johann Laurent, Alessandro Maresta, Krzysztof Narkiewicz, Ji-Guang Wang, Michael A. Weber, and John M. Flack.
Saturday, October 10, 2:30 PM | Abstract session 17 | Number 72

Join Idorsia at leading cardiovascular and kidney congresses
Idorsia will also be present at major US congresses, where it will host exhibitor spotlight sessions on “The Next Era in the Treatment of Hypertension.”

• AHA Hypertension, Crystal City, VA, October 8-10. Visit us at Tables 25 and 26. Exhibitor Spotlight at Ballroom A & B on Friday, October 9, from 1:00 to 1:30 p.m.
• ASN Kidney Week, Denver, CO, October 22-24. Visit us at Booth #1023. Exhibitor Spotlight at Theater #3 on Saturday, October 24, from 11:00 to 11:45 a.m.
• AHA Scientific Sessions, Chicago, IL, November 7-9. Visit us at Booth #3014. Exhibitor Spotlight at Learning Studio #3 on Sunday, November 8, from 9:30 to 10:15 a.m.

Notes to the editor

About Dr Michael A. Weber, MD
Dr. Weber is Professor of Medicine at the SUNY Downstate College of Medicine in Brooklyn, New York. He received his medical degree from Sydney University in Australia. His career has been focused primarily on hypertension and preventive cardiology. He has published numerous research articles in medical literature and has authored or edited several books.

Dr. Weber was the Editor-in-Chief of The Journal of Clinical Hypertension for over 10 years. Dr. Weber was one of the founders of The American Society of Hypertension and has served as its President. He also served as Chair of the ASH Hypertension Specialists Program. He is a Fellow of The American College of Physicians, The American College of Cardiology and The American Heart Association. He has served on the Cardiovascular and Renal Drugs Advisory Board of the Food and Drug Administration. He has also served for ten years as Chairman of the Formulary Committee of a major pharmacy benefits provider serving many of the leading health plans in the United States.

His main current research interests are in clinical trials of patients at high risk of cardiovascular events or strokes. He is also participating actively in trials in patients with metabolic disorders such as diabetes and kidney disease. Dr. Weber currently serves on the Steering Committees of several national and international clinical trials. Dr. Weber serves as a consultant to Idorsia.

About Dr. John M. Flack, MD
Dr. Flack, an Alpha Omega Alpha (AOA) graduate of the University of Oklahoma School of Medicine, is the Sergio Rabinovich Endowed Chair of Internal Medicine and the Professor and Chair of the Departments of Medicine and Population Science at Southern Illinois University School of Medicine. He is also Director of the Hypertension Clinic.

He is a board-certified Internal Medicine specialist and an internationally renowned hypertension specialist/cardiovascular epidemiologist with widely recognized clinical/research expertise in hypertension in African Americans, resistant/refractory hypertension, device-based therapies for hypertension and racial cardiovascular health disparities. Dr. Flack is the current President of the American Hypertension Specialist Certification Program. He has published over 250 peer-reviewed manuscripts and book chapters and is an Associate Editor for the journal Hypertension. He maintains an active clinical practice in complex hypertension at SIU where he teaches and mentors medical students and residents and undertakes innovative, cutting-edge research.

Dr. Flack has received numerous awards including the Distinguished Research Award (1993) from the International Society on Hypertension in Blacks (ISHIB), the Daniel D. Savage Memorial Scientific Award (1998) from the Association of Black Cardiologist (ABC), the F. Dewey Dodrill Award for Excellence (2007) from the American Heart Association (AHA), the Detroit News Michiganian of the Year (2009), and the University of Oklahoma Academic Physician of the Year (2012). Also, he has been repeatedly named to Top Doctor, Best Doctor, and Super Doctor lists. Previously, he served as a voting member of the FDA Cardio-Renal Advisory Board. Dr. Flack was recently conferred the status of Master by the American College of Physicians (ACP); he also previously served as a member of the ACP Board of Regents. Dr. Flack serves as a consultant to Idorsia.

About aprocitentan
Aprocitentan is a 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 antihypertensive drugs, to lower blood pressure in adult patients who are not adequately controlled on other drugs, 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, Switzerland, and Canada.

About PRECISION^6,7 (NCT03541174)
PRECISION was a multicenter, blinded, randomized, parallel-group, Phase 3 study, which was performed 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.

References

1. Parvanova A, et al. Mechanisms and treatment of obesity-related hypertension. Part 2: Treatments. Clin Kidney J. 2025;18(3):sfaf035. doi:10.1093/ckj/sfaf035.
2. Weil BR, et al. Enhanced endothelin-1 system activity with overweight and obesity. Am J Physiol Heart Circ Physiol. 2011;301(3):H689-H695. doi:10.1152/ajpheart.00206.2011.
3. Mavromatis LA, et al. Epidemiology of cardiovascular-kidney-metabolic syndrome. Nat Rev Nephrol. Published online May 7, 2026. doi:10.1038/s41581-026-01078-w.
4. Chen Y, et al. Prevalence and mortality association of different stages of cardiovascular-kidney-metabolic syndrome. JACC Adv. 2025;4(6 Pt 2):101843. doi:10.1016/j.jacadv.2025.101843.
5. McCormack T, et al. Uncontrolled Hypertension Prevalence, Characteristic Profiles, and Risk of Cardiorenal and Metabolic Outcomes: Insights from the EnligHTN Study. Adv Ther. Published online July 13, 2026. doi:10.1007/s12325-026-03681-6
6. Danaietash P et al. Identifying and treating resistant hypertension in PRECISION: A randomized long-term clinical trial with aprocitentan. J Clin Hypertension 2022 Jul;24(7):804-813.
7. Schlaich MP, et al. A randomized controlled trial of the dual endothelin antagonist aprocitentan for resistant hypertension. The Lancet, 2022; Dec 3;400(10367):1927-1937.

About Idorsia
The purpose of Idorsia is to discover, develop and commercialize innovative medicines to help more patients. To achieve this, we will develop Idorsia into a leading biopharmaceutical company, with a strong scientific core.

Headquartered near Basel, Switzerland – a European biotech hub – Idorsia has a highly experienced team of dedicated professionals, covering all disciplines from bench to bedside; QUVIVIQ™ (daridorexant), a different kind of insomnia treatment with the potential to revolutionize this mounting public health concern; strong partners to maximize the value of our portfolio; a promising in-house development pipeline; and a specialized drug discovery engine focused on small-molecule drugs that can change the treatment paradigm for many patients. Idorsia is listed on the SIX Swiss Exchange (ticker symbol: IDIA).

For further information, please contact:
Investor & Media Relations
Idorsia Pharmaceuticals Ltd, Hegenheimermattweg 91, CH-4123 Allschwil
+41 58 844 10 10
investor.relations@idorsia.com – media.relations@idorsia.com – www.idorsia.com

The above information contains certain "forward-looking statements", relating to the company's business, which can be identified by the use of forward-looking terminology such as “intend”, "estimates", "believes", "expects", "may", "are expected to", "will", "will continue", "should", "would be", "seeks", "pending" or "anticipates" or similar expressions, or by discussions of strategy, plans or intentions. Such statements include descriptions of the company's investment and research and development programs, business development activities and anticipated expenditures in connection therewith, descriptions of new products expected to be introduced by the company and anticipated customer demand for such products and products in the company's existing portfolio. Such statements reflect the current views of the company with respect to future events and are subject to certain risks, uncertainties and assumptions. Many factors could cause the actual results, performance or achievements of the company to be materially different from any future results, performances or achievements that may be expressed or implied by such forward-looking statements. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those described herein as anticipated, believed, estimated or expected. Idorsia has transferred its rights for aprocitentan, cenerimod and selatogrel to Idorsia Investments SARL to allow the repayment of notes issued in connection with the repurchase offer completed in August 2025. More details on the transfer can be found in the latest Financial Report.

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