RegulationOrphan Drug (United States), Orphan Drug (Japan), Overseas New Drugs Urgently Needed in Clinical Settings (China), Priority Review (China), Special Review Project (China)

Structure/Sequence

Molecular FormulaC27H31N5O7S

InChIKeySXTRWVVIEPWAKM-UHFFFAOYSA-N

CAS Registry157212-55-0

167

Clinical Trials associated with Bosentan

NCT06957002

/ Not yet recruitingPhase 2IIT

Bosentan in the Treatment of Giant Cell Arteritis. Multicenter, Randomized, Controlled, Superiority Phase II Trial Comparing a Combination of Bosentan and Glucocorticoids Versus Glucocorticoids Alone in the Treatment of Patients With GCA

The purpose of this study is to determine whether a treatment with 3 months of bosentan associated to standard therapy might be superior to glucocorticoids alone in term of failure free survival at 12 months

Start Date01 Sep 2025

Sponsor / Collaborator

Assistance Publique des Hôpitaux de Paris SA

NCT07081932

/ CompletedPhase 1

The Effect of Multiple Oral Doses of Bosentan on the Single Oral Dose Pharmacokinetics of Nerandomilast in Healthy Male Subjects (an Open-label, Two-treatment, Two-period Fixed Sequence Trial)

The main objective of this trial is to investigate the effect of bosentan, a moderate Cytochrome P450 (CYP) 3A inducer on the single dose pharmacokinetics of nerandomilast.

Start Date26 Aug 2025

Sponsor / Collaborator

Boehringer Ingelheim GmbH

NCT06887062

/ RecruitingPhase 2IIT

Dapagliflozin and Endothelin Receptor Antagonism in Large Vessel Vasculitis (DERAIL-LVV)

Large vessel vasculitis (LVV) is a disease that causes damage to blood vessels. This damage to blood vessels can increase the risk of patients with LVV developing cardiovascular disease, including heart attacks and strokes. A chemical produced in the body called endothelin may contribute to this increase in cardiovascular disease risk by causing the vessels to stiffen and blood pressure to increase.
It has previously been shown that by blocking the effects of endothelin, vessel stiffness and blood pressure improve. Bosentan is a tablet that blocks the effects of endothelin.
Dapagliflozin is a sodium-glucose co-transporter 2 inhibitor that has been shown to improve blood vessel function and stiffness in patients with diabetes.
The investigators plan to assess blood vessel function in those with LVV and participants without LVV. Participants with LVV will be given Bosentan and Dapagliflozin for 6 weeks, followed by Dapagliflozin for 4 weeks, to evaluate their impact on blood vessel function.

Start Date21 Mar 2025

Sponsor / Collaborator

The University of Edinburgh

100 Clinical Results associated with Bosentan

100 Translational Medicine associated with Bosentan

100 Patents (Medical) associated with Bosentan

3,131

Literatures (Medical) associated with Bosentan

31 Dec 2026·ANNALS OF MEDICINE

Heterogeneity in the efficacy of bosentan for hypertensive nephropathy: a study on individualized benefit prediction models based on pathological subtyping and dynamic trajectories

Article

Author: Wang, WanLing ; Huang, MengJie ; Chen, XiangMei ; Yu, Xiang ; Gong, XinYan ; Cai, GuangYan ; Ji, YuWei ; Nie, SaSa ; Wu, RiLiGe ; Wang, BaoLong ; Feng, Zhe

BACKGROUND:

Many patients with hypertensive nephropathy progress to chronic kidney disease (CKD). Targeting the core pathophysiological pathway of endothelin-1 activation, this study aimed to elucidate response patterns to the endothelin receptor type A/B (ETA/ETB) antagonist bosentan and construct a personalized prediction model.

METHODS:

This single-centre retrospective cohort study enrolled 166 patients with hypertension-related nephropathy confirmed by renal biopsy. Risk stratification was performed based on a pathological injury scoring. Three efficacy trajectories were identified using latent variable growth mixture models. Efficacy drivers were screened via random forest algorithms. Finally, early response thresholds were established using receiver operating characteristic (ROC) curves.

RESULTS:

Patients in the high-damage group exhibited significantly lower creatinine reduction than those in the low-damage group. Trajectory analysis revealed three patterns: sustained improvement (65.1%), with a 12-month creatinine reduction of 110.8 μmol/L, and deterioration (12.0%), with a deterioration inflection point at 5.3 ± 1.7 months and a subsequent creatinine increase of 40.2 μmol/L. Pathological injury score was the primary determinant of efficacy and was significantly negatively correlated with creatinine reduction (r = -0.61). Early response threshold analysis indicated that ΔCr_3M ≥ 42.3 μmol/L predicted 12-month efficacy, with an area under the curve (AUC) of 0.79. The early target-achievement group demonstrated significantly greater creatinine reduction than the nonachievement group. Compared with the non-sodium-glucose cotransporter-2 inhibitor (SGLT2i) group, the SGLT2i group demonstrated a 59% reduction in creatinine, while the diabetic subgroup showed a 47.1% smaller reduction than the nondiabetic subgroup.

CONCLUSIONS:

Bosentan may improve glomerular haemodynamics in patients with hypertensive nephropathy. We propose pathological and early-response thresholds that could guide dynamic, precision interventions before critical inflection points, potentially paving the way for an upgrade from static to proactive management. These findings require validation in larger cohorts.

01 Mar 2026·PEDIATRIC NEPHROLOGY

From RAAS blockade to regenerative medicine: evolving treatment strategies in Alport syndrome

Review

Author: Kim, Jin-Ju ; Lo Re, Claudia ; Fornoni, Alessia

Abstract:

Alport syndrome (AS) is a hereditary glomerulopathy caused by mutations in the COL4A3 , COL4A4 , or COL4A5 genes, leading to progressive kidney decline and extrarenal manifestations. Advances in genetic testing have enabled the reclassification of AS into X-linked, autosomal recessive, and autosomal dominant forms, facilitating more accurate diagnosis and risk stratification. While renin-angiotensin-aldosterone system (RAAS) blockade remains the foundation of treatment to delay kidney failure, it does not directly target the underlying molecular pathology. Adjunctive commercially available metabolic modulators, including SGLT2i, mineralocorticoid receptor antagonists, ezetimibe and GLP-1 receptor agonists, may offer additional kidney protection. Ameliorating therapies being tested in Phase II trials include endothelin receptor antagonists (e.g., atrasentan), dual endothelin receptor antagonist and angiotensin II receptor inhibition (e.g., sparsentan) FXR agonists (e.g., vonafexor), inducers of cholesterol efflux (e.g., VAR200 and R3R01), and NOX1/4 inhibitors (e.g., setanaxib), several of which are currently being evaluated in clinical trials. Novel strategies such as exon skipping, gene editing, and nonsense mutation readthrough (e.g., ELX-02) are advancing toward precision medicine approaches as disease modifying agents targeting the genetic cause of AS. Moreover, therapies targeting mitochondrial function, such as mitophagy enhancers, have demonstrated preclinical promise. Stem cell-based approaches are also being explored for their regenerative and anti-fibrotic effects. This review summarizes the current landscape of AS classification and treatment, highlighting both standard interventions and experimental therapies. Emphasis is placed on the molecular mechanisms underlying podocyte injury and fibrosis, recent preclinical findings, and ongoing clinical trials that may shift future therapeutic paradigms. Graphical abstract

01 Feb 2026·SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY

The application of infrared spectroscopy and DFT calculations to better understand interactions between bosentan hydrate and sildenafil base induced by high energy ball milling

Article

Author: Krupa, A ; Osiecka-Drewniak, N ; Górska, N ; Adamczyk, O ; Zając, W ; Juszyńska-Gałązka, E

In this study, infrared spectroscopy investigations in combination with DFT calculations were used to elucidate interactions between bosentan monohydrate (BOS) and sildenafil base (SIL) initiated under high energy ball milling. The research was focused mainly on the vibrational properties of their co-milled binary solid dispersions compared to the physical mixtures and single drugs. First, the stability and structure of sildenafil isomers were established. Theoretical infrared spectra were also calculated for trimers and tetramers of bosentan monohydrate and they were compared to the experimental data. The results revealed shifts in wavenumbers, primarily related to the presence of hydrogen bonds, water interactions, and molecular rearrangements during the optimization process of DFT procedure. Second, the infrared spectral analysis was carried out for co-milled binary formulations. The results showed significant changes in their vibrational dynamics related to the amorphization of crystalline drugs. Importantly, it was stated that the amorphous form was stabilized by hydrogen bonds created between BOS and SIL molecules. The classification of the spectra revealed distinct vibrational characteristics typical of binary amorphous solid dispersions. Importantly, the unique spectral classifications differed significantly from those of the corresponding physical mixtures. Finally, it was concluded that the mechanical activation of BOS and SIL base molecules under high energy ball milling resulted in a physical modification of their structure, which could translate into drug dissolution enhancement.

145

News (Medical) associated with Bosentan

05 Jan 2026

·www.biospace.com

Idorsia’s JERAYGO (aprocitentan) approved in Canada for the treatment of resistant hypertension

Idorsia receives approval from Health Canada for JERAYGO ™ (aprocitentan) as the first and only endothelin receptor antagonist (ERA) for the treatment of resistant hypertension. JERAYGO is a new oral antihypertensive therapy – the first systemic hypertension treatment to target a new pathway in over 30 years. Allschwil, Switzerland – January 5, 2026 Idorsia Ltd (SIX: IDIA) announces that Health Canada has granted marketing authorization for JERAYGO ™ (aprocitentan) for the treatment of resistant hypertension in adult patients in combination with at least three antihypertensive medicinal products. 1 The recommended dose is 12.5 mg orally once daily. The dose can be increased to 25 mg once daily for patients tolerating the 12.5 mg dose and in need of tighter blood pressure (BP) control. 1 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. Approximately 10% of hypertensive patients have resistant hypertension 3 , 4 – defined by uncontrolled blood pressure despite receiving at least three antihypertensive medications from different classes, at optimal doses – underscoring the urgent need for more effective therapies. Srishti Gupta, MD, Chief Executive Officer of Idorsia, commented: “JERAYGO is the first and only hypertension treatment to target the endothelin pathway, a fundamental yet previously unaddressed driver of disease onset, progression, and complications. The results of PRECISION show that targeting the endothelin pathway is crucial to adequately manage uncontrolled blood pressure. JERAYGO has demonstrated rapid, durable, and clinically significant double-digit blood pressure reduction across a broad spectrum of challenging patient populations, including those with obesity, chronic kidney disease, or type 2 diabetes. I am very proud of our team for achieving this milestone.” Idorsia is engaged in discussions to maximize the ability to make JERAYGO available to patients. For more information on the marketing authorization of JERAYGO in Canada and important safety information, please review the Product Monograph . Notes to the editor About the Phase 3 PRECISION study 1,5 The efficacy of aprocitentan was evaluated in one randomized, double-blind (DB), placebo-controlled Phase 3 multicenter study. Patients with uncontrolled blood pressure (systolic blood pressure [SBP] ≥140 mmHg) despite the use of at least three antihypertensive medicinal products and following exclusion of pseudo-resistant hypertension (e.g., white coat effect, inappropriate blood pressure measurement, secondary causes of hypertension) were considered to have resistant hypertension. The patients were switched to standardized background antihypertensive therapy consisting of an angiotensin receptor blocker (valsartan 160 mg), a calcium channel blocker (amlodipine 5 or 10 mg), and a diuretic (hydrochlorothiazide 25 mg) throughout the study. Patients with concomitant use of beta-blockers continued this treatment throughout the study, in addition to the standardized background antihypertensive therapy and study treatment. A total of 730 patients received either aprocitentan 12.5 mg, aprocitentan 25 mg, or placebo once daily during the initial 4-week DB treatment (part 1). Thereafter, patients received aprocitentan 25 mg once daily during the 32-week single-blind treatment (part 2). At the end of the 32 weeks, patients were re-randomized to receive either aprocitentan 25 mg or placebo, once daily, during the 12-week double-blind withdrawal (DB-WD) treatment (part 3). The primary efficacy endpoint was the change in sitting SBP (SiSBP) from baseline to Week 4 during DB treatment (part 1), measured at trough by unattended automated office blood pressure (uAOBP). The key secondary endpoint was the change in SiSBP measured at trough by uAOBP from DB-WD baseline (Week 36) to Week 40 (part 3). Patients had a mean age of 61.7 years (range 24 to 84 years; 34.1% were ≥ 65 and < 75 years; 9.9% were ≥ 75 years) and 59.5% were male. Patients were White (82.9%), African American (11.2%) or Asian (5.2%). The mean body weight was 97.6 kg (range 46 to 196 kg) and mean BMI was 33.7 kg/m2 (range 18 to 64 kg/m2). Patients had a medical history of type 2 diabetes mellitus (54.1%), ischemic heart disease (30.8%), central nervous system vascular disorders (23.0%), chronic kidney disease stages 3 and 4 (22.2%; 19.3% of patients had eGFR 30–59 mL/min/1.73 m2 and 2.9% had eGFR 15–29 mL/min/1.73 m2), congestive heart failure (19.6%), and sleep apnea syndrome (14.1%). 63.0% of patients had four or more antihypertensive medicinal products. Key PRECISION findings 1,5 Doses of aprocitentan 12.5 and 25 mg showed a statistically significant reduction vs placebo on SiSBP at Week 4. The treatment effect was consistent for sitting diastolic blood pressure (SiDBP). The persistence of the BP-lowering effect of aprocitentan was shown in DB-WD treatment (part 3). In patients re-randomized to placebo, the mean SiSBP increased, whereas in patients re-randomized to aprocitentan 25 mg the mean effect on SiSBP was stable, resulting in a statistically significant difference. The treatment effect was consistent for SiDBP. The effect was also consistent across SBP and DBP measured by ambulatory BP monitoring (ABPM) and assessed as daytime, night-time, and 24h periods at Week 4 and Week 40. A substantial proportion (i.e., at least 90%) of the BP-lowering effect was observed within the first two weeks of treatment with aprocitentan. The effect of aprocitentan was consistent across subgroups of age (including patients ≥ 75 years), sex, race (including patients with Black or African American origin), BMI, baseline urine albumin-to-creatinine ratio (UACR), baseline eGFR and medical history of diabetes. The most frequently reported adverse reactions with aprocitentan were edema/fluid retention (mostly peripheral edema) (9.1%, 12.5 mg; 18.4%, 25 mg) and hemoglobin decreased (3.7%, 12.5 mg; 1.2%, 25 mg). JERAYGO is contraindicated for use in women who are pregnant, breast-feeding, in women of childbearing potential who are not using reliable contraception, patients with severe hepatic impairment, and in patients with hypersensitivity to the active substance or to any of the excipients. About aprocitentan Aprocitentan is Idorsia’s once-daily, orally active, dual endothelin receptor antagonist, which inhibits the binding of ET-1 to ET A and ET B 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. Aprocitentan is approved as JERAYGO™ for the treatment of resistant hypertension in combination with at least three antihypertensives in the European Union, the UK, and Switzerland, and now in Canada. Idorsia Pharmaceuticals Ltd has transferred its rights for aprocitentan (including JERAYGO™) 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 press release issued on May 21, 2025 and on the exchange offer in the press release issued on August 27, 2025. References JERAYGO ™ Product Monograph NCD Risk Factor Collaboration (NCD-RisC). Worldwide trends in hypertension prevalence and progress in treatment and control from 1990 to 2019: a pooled analysis of 1201 population-representative studies with 104 million participants. Lancet 2021; 398:957-80. Noubiap JJ, et al. Global prevalence of resistant hypertension: a meta-analysis of data from 3·2 million patients. Heart 2019; 105: 98–105. Williams B, et al. 2018 ESC/ESH guidelines for the management of arterial hypertension. Eur Heart J 2018; 39: 3021–104. 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 challenge accepted medical paradigms, answering the questions that matter most. To achieve this, we will discover, develop, and commercialize transformative medicines – either with in-house capabilities or together with partners – and evolve 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 – 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. Attachment Press Release PDF

Clinical ResultDrug ApprovalPhase 3

10 Dec 2025

·www.globenewswire.com

New Hypertension publication underscores aprocitentan’s potential in managing hypertension patients with CKD

New analysis from landmark Phase 3 PRECISION trial published in Hypertension highlights the renal-protective benefits of aprocitentan in addition to the marked reduction in blood pressure in a high-risk CKD population with difficult-to-control hypertension Allschwil, Switzerland – December 10, 2025Idorsia Ltd (SIX: IDIA) announced the publication of a new analysis from the landmark Phase 3 PRECISION study in Hypertension titled “Aprocitentan in Patients with Chronic Kidney Disease and Resistant Hypertension”.1 The analysis examined the efficacy and safety of aprocitentan (TRYVIO™/JERAYGO™) in patients with chronic kidney disease (CKD) and confirmed resistant hypertension – a population with very limited treatment options and high cardiovascular and renal risk. Aprocitentan, the first approved antihypertensive targeting the endothelin pathway, was well tolerated. It significantly reduced both office and nighttime ambulatory blood pressure (BP), as well as markedly lowered albuminuria – a key marker of kidney damage – without increasing the risk of hyperkalemia. Patrick Rossignol, MD, PhD, nephrologist, Head of the Medical Specialties and nephrology departments at the Princess Grace Hospital, Monaco, commented:“Hypertension is both a cause and consequence of chronic kidney disease (CKD) and managing it in these patients is particularly challenging. Blood pressure is often difficult to control, and many antihypertensive agents carry risks of worsening renal function or causing hypo or hyperkalemia, which are all associated with dismal outcomes. The data presented in this manuscript are truly transformative for our patients: aprocitentan not only markedly lowered blood pressure but also reduced proteinuria by up to 60% on top of standardized background triple therapy including valsartan and a thiazide-like diuretic – without inducing dyskalemia or worsening renal function. Its favorable safety profile and exceptionally low discontinuation rate after nearly one year of treatment position aprocitentan as a fundamental advancement for patients with CKD and treatment resistant hypertension.” Martine Clozel, MD, Chief Scientific Officer and Head of Research at Idorsia, commented: “The PRECISION study included patients with confirmed resistant hypertension without excluding patients with stage 3 or 4 chronic kidney disease (CKD), as these patients are particularly underserved. The endothelin pathway plays a clear role in both kidney dysfunction and hypertension, yet until aprocitentan, no antihypertensive therapy targeted this pathway – explaining why many patients were not responding to treatment. TRYVIO/JERAYGO blocks the two endothelin receptor subtypes fundamental in its actions. In patients who had often tried more than four antihypertensive drugs, aprocitentan delivered significant blood pressure reductions alongside a major antiproteinuric effect, suggesting meaningful renal protection.” 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 In patients with CKD, hypertension significantly contributes to preventable morbidity and mortality and is a leading cause of cardiovascular disease.5-7 In 2019, there were more than 650 million people with CKD worldwide and 1.2 million deaths due to CKD.8 Especially nocturnal hypertension has been associated with increased cardiovascular morbidity.9-11 Therefore, appropriate and effective management of hypertension is a key strategy of managing patients with CKD.12,13 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-1.14 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.15,16 Upregulation of endothelin-1 is considered an important contributor to the pathophysiology of CKD progression, including increased blood pressure, glomerular membrane permeability, mesangial cell proliferation, podocyte dysfunction, interstitial inflammation and fibrosis.17,18 About the analysis1The Phase 3 PRECISION study evaluated aprocitentan in 730 patients with confirmed resistant hypertension. This post-hoc analysis focused on the 147 participants with CKD categorized as high or very high risk according to KDIGO criteria.19 At Week 4, aprocitentan 12.5 mg and 25 mg reduced office systolic BP by –13.5 mm Hg and –16.6 mm Hg, respectively, versus –4.4 mm Hg with placebo – with reductions sustained with aprocitentan 25 mg through Week 36 (-16.4 mm Hg)Nighttime ambulatory systolic BP – a strong predictor of cardiovascular and renal outcomes and often poorly controlled in CKD – was reduced by –9.6 mm Hg and –13.8 mm Hg, respectively, versus –2.5 mm Hg with placebo.UACR – a marker of kidney damage and progression – was reduced by –47.1% and –59.6%, respectively, versus –2.4% with placebo – with reductions associated with improved long-term prognosis sustained through Week 36 (–61.6%).Aprocitentan was generally well tolerated. The most common adverse event was mild-to-moderate peripheral edema, typically seen early on and managed with diuretic adjustment. No significant changes in potassium or estimated glomerular filtration rate (eGFR) were observed. About aprocitentanAprocitentan 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 PRECISION20,21 (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 findings21 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<0.0001). Office DBP also increased with placebo compared to aprocitentan (5.2 mmHg; p<0.001). The difference between the two groups remained up to week 48. The results from ambulatory BP monitoring, a strong predictor of cardiovascular mortality,1,2 confirmed those derived from office measurements. At the end of Part 1, aprocitentan, after placebo correction, decreased both the 24-hour ambulatory SBP (–4.2 mmHg for the 12.5 mg dose and –5.9 mmHg for the 25 mg dose) and DBP (–4.3 mmHg for the 12.5 mg dose and –5.8 mmHg for the 25 mg dose). The placebo-corrected SBP lowering effect was –5.1 mmHg and –7.4 mmHg during the nighttime and –3.8 mmHg and –5.3 mmHg during the daytime, for the 12.5 mg and 25 mg doses, respectively. In Part 3, after 4 weeks of withdrawal (week 40), both the 24-hour ambulatory SBP and DBP increased with placebo compared with aprocitentan (6·5 mm Hg and 6·8 mm Hg respectively). Treatment-emergent adverse events (TEAEs) during the 4-week double-blind study period (Part 1) were reported in 27.6% and 36.7% of the patients treated with 12.5 and 25 mg aprocitentan, respectively, versus 19.4% in the placebo group. The most frequent adverse event was fluid retention which was reported more frequently with aprocitentan than with placebo in a dose-dependent fashion (9.1%, 18.4%, and 2.1% for patients receiving aprocitentan 12.5 mg, 25 mg and placebo, during Part 1, respectively; 18.2% for patients receiving aprocitentan 25 mg during Part 2; and 2.6% and 1.3% for patients on aprocitentan 25 mg and placebo, during Part 3, respectively). Fluid retention was generally mild-to-moderate, was primarily peripheral edema and was manageable by current clinical practice including use of diuretics. Discontinuation due to edema/fluid retention was reported for seven patients. Notes to the editor About Dr Patrick Rossignol, MD, PhDPatrick Rossignol is a nephrologist and vascular medicine specialist, European Society of Hypertension-certified hypertension specialist and formerly a Professor of Therapeutics at the University of Lorraine, France. Since 2022, he is heading the Department of Medicine specialties and nephrology-hemodialysis at the Princess Grace Hospital, in Monaco. He is also the medical director of the private hemodialysis Centre, in Monaco. He is chairing Monaco Clinical Research Infrastructure Network (M-CRIN) since its creation in 2025.He is the Coordinator of the FCRIN INI-CRCT (Cardiovascular and Renal Clinical trialists network of excellence www.inicrct.fr,) since its creation 2014, FCRIN being the “French Clinical research Infrastructure network”. From 2018 to 2022, he used to be the Director of the Nancy University Hospital INSERM Clinical Investigation Centre, after serving as its Deputy Director for ten years. He is now an associate researcher. He is also the Kidney Disease Clinical Trialists (KDCT) workshop course director. Professor Rossignol has been involved in numerous clinical trials in the settings of heart failure, hypertension and chronic kidney disease as well as in translational basic research studies on the cardiorenal syndrome. He has published more than 700 peer-reviewed publications and is co-inventor of 9 biomarker international patents in the cardiorenal syndrome setting. Prof Rossignol used to serve as a consultant to Idorsia while he was chairing the PRECISION trial critical event committee. References Rossignol P, et al. Aprocitentan in Patients With Chronic Kidney Disease and Resistant Hypertension. Hypertension. Online ahead of print, December 2025, doi.org/10.1161/HYPERTENSIONAHA.125.25563World Health Organization. Global report on hypertension 2025: high stakes: turning evidence into action. 2025.Murray, Christopher J L. Findings from the Global Burden of Disease Study 2021. The Lancet. 2024; 403 (10440): 2259 - 2262Carey RM, et al. Prevalence of Apparent Treatment-Resistant Hypertension in the United States. Hypertension. 2019;73(2):424-431Rossignol P, Massy ZA, Azizi M, et al. The double challenge of resistant hypertension and chronic kidney disease. Lancet. 2015;386(10003):1588-1598.Bakris G, Chen C, Campbell AK, Ashton V, Haskell L, Singhal M. Real-World Impact of Blood Pressure Control in Patients With Apparent Treatment-Resistant or Difficult-to-Control Hypertension and Stages 3 and 4 Chronic Kidney Disease. Am J Hypertens. 2024;37(6):438-446.Kidney Disease: Improving Global Outcomes Blood Pressure Work G. KDIGO 2021 Clinical Practice Guideline for the Management of Blood Pressure in Chronic Kidney Disease. Kidney Int. 2021;99(3S):S1-S87.Liu Y, He Q, Li Q, et al. Global incidence and death estimates of chronic kidney disease due to hypertension from 1990 to 2019, an ecological analysis of the global burden of diseases 2019 study. BMC Nephrol. 2023;24(1):352.Huart J, Persu A, Lengele JP, Krzesinski JM, Jouret F, Stergiou GS. Pathophysiology of the Nondipping Blood Pressure Pattern. Hypertension. 2023;80(4):719-729.Dolan E, Stanton A, Thijs L, et al. Superiority of ambulatory over clinic blood pressure measurement in predicting mortality: the Dublin outcome study. Hypertension. 2005;46(1):156-161.Hansen TW, Li Y, Boggia J, Thijs L, Richart T, Staessen JA. Predictive role of the nighttime blood pressure. Hypertension. 2011;57(1):3-10.Kreutz R, Brunstrom M, Burnier M, et al. 2024 European Society of Hypertension clinical practice guidelines for the management of arterial hypertension. Eur J Intern Med. 2024;126:1-15.Kidney Disease: Improving Global Outcomes CKDWG. KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Kidney Int. 2024;105(4S):S117-S314.Kedzierski RM, et al. Endothelin system: the double-edged sword in health and disease. Annu Rev Pharmacol Toxicol. 2001; 41:851-76.Iglarz M, et al. At the heart of tissue: endothelin system and end-organ damage. Clin Sci 2010; 119:453-63.NCD Risk Factor Collaboration (NCD-RisC). Worldwide trends in hypertension prevalence and progress in treatment and control from 1990 to 2019: a pooled analysis of 1201 population-representative studies with 104 million participants. Lancet 2021; 398:957-80.Smeijer JD, Kohan DE, Dhaun N, Noronha IL, Liew A, Heerspink HJL. Endothelin receptor antagonists in chronic kidney disease. Nat Rev Nephrol. 2024.Dhaun N, Webb DJ, Kluth DC. Endothelin-1 and the kidney--beyond BP. Br J Pharmacol. 2012;167(4):720-731.Kidney Disease: Improving Global Outcomes CKDWG. KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Kidney Int. 2024;105(4S):S117-S314.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.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 IdorsiaIdorsia Ltd is reaching out for more – we have more passion for science, we see more opportunities, and we want to help more patients. The purpose of Idorsia is to challenge accepted medical paradigms, answering the questions that matter most. To achieve this, we will discover, develop, and commercialize transformative medicines – either with in-house capabilities or together with partners – and evolve 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 RelationsIdorsia Pharmaceuticals Ltd, Hegenheimermattweg 91, CH-4123 Allschwil+41 58 844 10 10investor.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 "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 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. Attachment Press Release PDF

Clinical ResultPhase 3Drug ApprovalAHA

05 Nov 2025

·www.idorsia.com

Idorsia to present new aprocitentan insights at ASN Kidney Week & AHA Scientific Sessions

New analysis confirms reductions in blood pressure and albuminuria by aprocitentan in patients with true resistant hypertension and high cardiovascular risk – including chronic kidney disease Allschwil, Switzerland – November 05, 2025Idorsia Ltd (SIX: IDIA) shares that new analysis of the landmark Phase 3 PRECISION study of aprocitentan, Idorsia’s endothelin receptor antagonist, will be presented at the American Society of Nephrology (ASN) Kidney Week 2025, taking place in Houston, TX, November 5–9, 2025. A poster presentation entitled “Is Aprocitentan's Effect on Albuminuria Merely Due to Lowered BP? Subgroup Analysis of the PRECISION Trial” will be held in the Hypertension and CVD: Clinical – 1 session on November 6, at 10:00-12:00 CT (Abstract). The poster highlights that aprocitentan, in addition to at least three antihypertensives, substantially reduced systolic blood pressure and Urine Albumin-to-Creatinine Ratio (UACR) versus placebo across all subgroups with renal impairment and resistant hypertension. The correlation analysis shows that the highly significant reductions in blood pressure with aprocitentan do not solely explain the observed reductions in UACR, suggesting that additional mechanisms are involved in aprocitentan’s renal-protective effect, such as a decrease in glomerular permeability, post-glomerular vasodilation or functional tubular changes. In addition, Idorsia will be present at The American Heart Association (AHA) Scientific Sessions 2025, taking place in New Orleans, LA, November 7–10, 2025, with a sponsored educational symposium entitled ‘The Next Era in the Treatment of Hypertension’. The symposium will take place in Learning Studio 1 on November 9, at 9:30am - 10:15am CT. Dr Michael Bloch, Associate Professor, Department of Internal Medicine at University of Nevada School of Medicine and Medical Director of Vascular Medicine and Anticoagulation Services at the Renown Medical Center Institute for Heart and Vascular Health, will present data from the PRECISION trial and discuss the use of aprocitentan in clinical practice. Notes to the editor About aprocitentanAprocitentan 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 IdorsiaThe purpose of Idorsia is to challenge accepted medical paradigms, answering the questions that matter most. To achieve this, we will discover, develop, and commercialize transformative medicines – either with in-house capabilities or together with partners – and evolve 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 RelationsIdorsia Pharmaceuticals Ltd, Hegenheimermattweg 91, CH-4123 Allschwil+41 58 844 10 10investor.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. Attachment Press Release PDF

Drug ApprovalAHAPhase 3

100 Deals associated with Bosentan

External Link

KEGG	Wiki	ATC	Drug Bank
D01227	Bosentan	C02KX01	DB00559

R&D Status

Approved

10 top approved records.

to view more data

Indication	Country/Location	Organization	Date
Ulcer	Japan	Actelion Pharmaceuticals Ltd.	24 Aug 2015
Familial Primary Pulmonary Hypertension	Australia	Janssen-Cilag Pty Ltd.	20 Nov 2002
Idiopathic pulmonary arterial hypertension	Australia	Janssen-Cilag Pty Ltd.	20 Nov 2002
Scleroderma associated digital ulcer	European Union	Janssen-Cilag International NV	14 May 2002
Scleroderma associated digital ulcer	Iceland	Janssen-Cilag International NV	14 May 2002
Scleroderma associated digital ulcer	Liechtenstein	Janssen-Cilag International NV	14 May 2002
Scleroderma associated digital ulcer	Norway	Janssen-Cilag International NV	14 May 2002
Pulmonary Arterial Hypertension	United States	Actelion Pharmaceuticals US, Inc.	20 Nov 2001

Developing

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Hypertension	Phase 3	Portugal	Actelion Pharmaceuticals Ltd.	27 Feb 2012
Asphyxia	Phase 3	Netherlands	Actelion Pharmaceuticals Ltd.	04 Aug 2011
Dyspnea	Phase 3	Netherlands	Actelion Pharmaceuticals Ltd.	04 Aug 2011
Persistent Fetal Circulation Syndrome	Phase 3	Netherlands	Actelion Pharmaceuticals Ltd.	04 Aug 2011
Heart Failure	Phase 3	Netherlands	Actelion Pharmaceuticals Ltd.	09 Nov 2010
Vascular Diseases	Phase 3	Netherlands	Actelion Pharmaceuticals Ltd.	09 Nov 2010
Connective Tissue Diseases	Phase 3	Canada	Actelion Pharmaceuticals US, Inc.	01 Apr 2009
Diabetes Mellitus, Type 2	Phase 3	Canada	Actelion Pharmaceuticals US, Inc.	01 Jan 2009
Diabetic Nephropathies	Phase 3	Canada	Actelion Pharmaceuticals US, Inc.	01 Jan 2009
Sarcoidosis	Phase 3	United States	Actelion Pharmaceuticals US, Inc.	01 Apr 2008

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04770155 (UMMC_Pilot, CTgov)	Early Phase 1	Ischemic Attack, Transient	8	Dietary Nitrates 400 mg (Beetroot Juice (Aim 1a))	ptjqkydeqt(tbamsxmjgw) = srjyczkvkj jdwyluniht (ehyzezuucn, qlrtqvwmlo - emjnuhanxm) View more	-	31 Oct 2023
				Dietary Nitrates 400 mg (Placebo (Aim 1a))	ptjqkydeqt(tbamsxmjgw) = qwurnurlwv jdwyluniht (ehyzezuucn, hfuaqeeqnl - ctihqeqlme) View more
EADV 12023 \| EADV 22023	Not Applicable	Vascular Diseases	-	Bosentan 62.5 mg	pwazgkanuc(nzggaydamf): mean treatment effect = 35.6 (95% CI, 13.4 - 57.7), P-Value = <0.05 View more	Positive	11 Oct 2023
				Nifedipine 20 mg
EULAR2019	Not Applicable	Scleroderma, Systemic	35	Bosentan	gmgzgpcdos(zzvqkaxece) = zckzrgwdap cuvmwslxew (vbchycdskp ) View more	Positive	12 Jun 2019
NCT00433329 (COMPASS-3, Pubmed \| Pulm Circ)	Phase 4	Pulmonary Arterial Hypertension Add-on	100	Bosentan monotherapy	tzdwhhapfx(mwbkeatlcu) = mkufxhlmbj dvhbpraiad (qcfcachach )	-	01 Jan 2018
				Add-on sildenafil	tzdwhhapfx(mwbkeatlcu) = lifldqomvg dvhbpraiad (qcfcachach )
NCT01338415 (FUTURE 3 Ext, CTgov)	Phase 3	Pulmonary Arterial Hypertension	58	Bosentan (Bosentan 2mg/kg b.i.d.)	krfwcumktg = ykqnuaijkq yustvnfrrq (dftdxwjnpq, qzffrczqco - pykwhsgihe) View more	-	11 Dec 2017
				Bosentan (Bosentan 2mg/kg t.i.d.)	krfwcumktg = ymqyzfdaqr yustvnfrrq (dftdxwjnpq, zpmvcgzzzq - zafzaoufmb) View more
NCT00323297 (Pubmed \| BMC Cardiovasc Disord)	Phase 4	Pulmonary Arterial Hypertension	105	Sildenafil	hpcwqvxthq(vutuoijtxb) = nzftvoygiv uwtdblrcrc (draslfikto )	-	06 Sep 2017
				Placebo	hpcwqvxthq(vutuoijtxb) = uagmoepmum uwtdblrcrc (draslfikto )
ESC2017	Not Applicable	Hypertension, Pulmonary	-	Bosentan	iyibvdfxoq(yufwwumxpz) = xliiwqejsm mucpwqsftv (zzzofirhel ) View more	-	29 Aug 2017
				bosentan	iyibvdfxoq(yufwwumxpz) = bnesmwpgww mucpwqsftv (zzzofirhel ) View more
NCT01223352 (FUTURE 3, CTgov)	Phase 3	Familial Primary Pulmonary Hypertension \| Pulmonary Arterial Hypertension \| Idiopathic pulmonary arterial hypertension	64	Bosentan (Bosentan 2 mg/kg t.i.d.)	epfmrulzic = uginahpbik zhxjmftbvi (juaypaiktr, uefsbqhdek - usgrceoheo) View more	-	29 Jun 2017
				Bosentan (Bosentan 2 mg/kg b.i.d.)	yjsvdoqwjt = zfncdarwnz eyvojqqmen (xyyloglhru, fczyaeklmx - gmsmwnkmfe) View more
NCT00825266 (CTgov)	Phase 2	Pulmonary Arterial Hypertension \| Insulin Resistance	2	Bosentan (Bosentan)	rvrppvplje = ptumlczhjt oijewzxech (fqlsvcbplr, xgzubmmdmv - pmugumlvcq) View more	-	31 Mar 2017
				Pioglitazone (Pioglitazone)	rvrppvplje = dxyeyotwlo oijewzxech (fqlsvcbplr, wijvgfyxoj - exrrhpmlce) View more
NCT00319020 (FUTURE 2, CTgov)	Phase 3	Familial Primary Pulmonary Hypertension	33	Bosentan (Patients With Previous Bosentan)	xmhhrchxqs(auihpcxzfp) = ivzcoxpmtq cwvyjnofmo (nyfnbypnom, dbdlvkfzee - nentifrysn) View more	-	29 Mar 2017
				Bosentan (Bosentan-naive Patients)	xmhhrchxqs(auihpcxzfp) = ogcogvadct cwvyjnofmo (nyfnbypnom, rwgskxunxl - zwvavceqph) View more

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