Opsumit (macitentan) / Nippon Shinyaku, J&J - LARVOL DELTA

BUSULFAN ASSOCIATED PULMONARY TOXICITY AND INFECTIOUS COMPLICATIONS FOLLOWING AUTOLOGOUS SCT IN A 3-YEAR-OLD CHILD WITH NEUROBLASTOMA (EBMT 2026) - "Background: High-dose busulfan/melphalan (Bu/Mel) remains a standard conditioning regimen for autologous stem cell transplantation in high-risk neuroblastoma but is associated with significant organ toxicity, particularly hepatic and pulmonary injury...A treatment with Defibrotide, Ganciclovir and Azithromycin was initiated...We started a treatment with Sildenafil, Macitentan, Epoprostenol in addition to Methylprednisolone pulse therapy and antifibrotic treatment with Nintedanib, Hydroxychloroquin and Azithromycin... This case illustrates the complex interplay between infectious complications, post-transplant inflammation and busulfan-induced pulmonary toxicity in a young neuroblastoma patient undergoing Bu/Mel conditioning and autologous SCT. Consideration of busulfan toxicities, especially when presenting with nonspecific early symptoms is important even when alternative explanations such as severe infection may appear equally plausible after autologous SCT. Early..."

Clinical • Acute Respiratory Distress Syndrome • Cardiovascular • Cystic Fibrosis • Cytomegalovirus Infection • Gastroenterology • Genetic Disorders • Hepatology • Immunology • Infectious Disease • Inflammation • Interstitial Lung Disease • Neuroblastoma • Pneumonia • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • Septic Shock • Solid Tumor

Outcome of Pediatric Pulmonary Hypertension Patients Requiring ECMO (SCCM 2026) - "100% (31/31) of patients received at least one PAH therapy prior to and during ECMO [31/31 (100%) inhaled nitric oxide or inhaled epoprostenol; 26/31 (84%) sildenafil, tadalafil or riociugat; 18/31 (58%) macitentan, ambrisentan or bosentan; 8/31(26%) selexipag; 10/31(32%) treprostinil. Pediatric PAH is a complex disease due to varied etiologies often requiring multiple medications to effectively manage. Certain subpopulations such as those with single ventricle CHD have higher mortality especially when requiring ECMO. Further study is necessary to determine if earlier identification and management of PAH patients prior to ECMO can improve survival and decrease need for mechanical circulatory support in this high-risk population."

Clinical • Cardiovascular • Heart Failure • Hematological Disorders • Infectious Disease • Pediatrics • Pneumonia • Pulmonary Arterial Hypertension • Pulmonary Disease • Pulmonary Embolism • Respiratory Diseases

Comparative Effectiveness of Endothelin Receptor Antagonists and PDE-5 Inhibitors in PAH (SCCM 2026) - "Adults carrying an ICD-10 code for PAH (I27.0) who started either ERA monotherapy (bosentan, ambrisentan, macitentan) or PDE5I monotherapy (sildenafil, tadalafil) with no prior prostacyclin or combination therapy were eligible. n this large multicentre, propensity-matched analysis of treatment-naive PAH, ERAs and PDE5Is produced indistinguishable 12-month survival, cardiovascular outcomes, and adverse-event rates. These findings support current guidelines that either class is an acceptable first-line option; choice may therefore be guided by individual comorbidity profiles, side-effect tolerance, and cost rather than expectations of differential efficacy."

HEOR • Cardiovascular • Congestive Heart Failure • Heart Failure • Myocardial Infarction • Pulmonary Arterial Hypertension • Respiratory Diseases

OFF-LABEL SOTATERCEPT IN HIGH-RISK PULMONARY HYPERTENSION WITH LIVER DISEASE AND LIMITED THERAPEUTIC OPTIONS (ACC 2026) - "Background: Pulmonary arterial hypertension (PAH) and its portopulmonary variant (PoPH) are progressive disorders with high morbidity and limited treatment options, especially in advanced liver disease Case: A 60-year-old woman with severe precapillary PAH from PoPH and COPD overlap (WHO Group 1 & 3), complicated by alcoholic cirrhosis (Child-Pugh A→B) and chronic thrombocytopenia (platelets 70K), remained high risk (REVEAL 2.0 > 9) despite tadalafil, macitentan, and selexipag.She presented with dyspnea and severe precapillary PAH unresponsive to maximal oral therapy; baseline hemodynamics showed markedly elevated pulmonary pressures. Sotatercept delivered meaningful benefit without safety events in advanced PoPH/PAH with cirrhosis and limited options, supporting its potential as an adjunct in complex high-risk PAH and as a bridge optimization pre-transplant"

Cardiovascular • Chronic Obstructive Pulmonary Disease • Fibrosis • Hematological Disorders • Hepatology • Immunology • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • Thrombocytopenia

PHARMACOKINETICS (PK) AND SAFETY OF MACITENTAN 75 MG: PHASE I DATA FROM CHINESE AND WHITE HEALTHY ADULTS (ACC 2026) - P1, P3 | "No clinically relevant differences in PK were observed between Chinese and White participants after a single dose of macitentan 75 mg. The safety profile of macitentan 75 mg was consistent between studies and with the known profile of macitentan 10 mg."

Clinical • P1 data • PK/PD data • Cardiovascular • Pulmonary Arterial Hypertension • Respiratory Diseases

THROMBOCYTOPENIA ASSOCIATED THYROID HEMATOMA FOLLOWING WINREVAIR THERAPY (ACC 2026) - "Background: Winrevair (sotatercept-cskr), approved in 2024 for pulmonary arterial hypertension (PAH, WHO Group 1), is an activin signaling inhibitor that enhances exercise capacity and slows disease progression...Case: A 41-year-old patient with PAH, previously treated with treprostinil, riociguat, and macitentan, started Winrevair... This case underscores the risk of severe thrombocytopenia with Winrevair, leading to a thyroid hematoma post-biopsy. Vigilant platelet monitoring, stricter pre-procedure thresholds, and dose adjustments are critical to prevent complications in PAH patients."

Cardiovascular • Endocrine Disorders • Hematological Disorders • Pulmonary Arterial Hypertension • Respiratory Diseases • Thrombocytopenia

PLATYPUS: A Study Providing Treatment Access in Participants With Pulmonary Hypertension Completing a Parent Study and Having no Other Option (clinicaltrials.gov) - P3 | N=280 | Recruiting | Sponsor: Actelion | Trial completion date: Sep 2029 ➔ Feb 2028

Trial completion date • Cardiovascular • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

Long-Term Treatment with Single-Tablet Combination of Macitentan and Tadalafil in Pulmonary Arterial Hypertension: Results from A DUE and Its Open-Label Period. (PubMed, Adv Ther) - P3 | "Long-term treatment with single-tablet combination of macitentan/tadalafil was well tolerated, with no new safety findings identified. Most patients were alive at EOS. Incremental improvements in 6MWD and NT-proBNP observed in the DB with M/T FDC were sustained over 2 years."

Journal • Cardiovascular • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • NPPB

Unrepaired Truncus Arteriosus Type 1 With Eisenmenger Syndrome and Recurrent Embolic Strokes: An Adult Case Report. (PubMed, Am J Case Rep) - "A conservative management strategy was adopted, including dual antiplatelet therapy, sildenafil, macitentan, bisoprolol, and oxygen therapy. CONCLUSIONS This case highlights the exceptional natural course of uncorrected truncus arteriosus in adulthood. It underscores that for patients with Eisenmenger physiology where surgical repair is not feasible, a multidisciplinary approach focusing on tailored antithrombotic and pulmonary vasodilator therapies is essential for stroke prevention and clinical stability."

Journal • Cardiovascular • Hypertension • Ischemic stroke • Otorhinolaryngology • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • Vertigo

Management of Pulmonary Hypertension Due to Atrial Septal Defect and Acute Pulmonary Embolism with VA-ECMO (ISHLT 2026) - "She received diuretics, inhaled epoprostenol, and anti-coagulation, and was extubated day 9...IV treprostinil was started up to 20 ng/kg/min allowing for ECMO decannulation on day 25.She was transitioned to oral PH therapy (macitentan/sildenafil) with ASD closure deferred due to high PVR...She is now off oxygen, working, on combination pill macitentan/tadalafil.Summary VA-ECMO is a viable strategy for PH patients who develop refractory RV failure, as a bridge to lung transplantation or initiation of PH therapies. Careful patient selection and multidisciplinary management is essential."

Cardiovascular • Hypertension • Hypotension • Pulmonary Arterial Hypertension • Pulmonary Disease • Pulmonary Embolism • Respiratory Diseases • Thrombosis

MACITENTAN FOR PULMONARY ARTERIAL HYPERTENSION ASSOCIATED WITH SYSTEMIC SCLEROSIS: RESULTS FROM THE EUROPEAN SCLERODERMA TRIALS AND RESEARCH GROUP (EUSTAR) DATABASE (SSWC 2026) - "The EUSTAR database offers a unique opportunity to evaluate real-life data on macitentan treatment patterns in SSc-PAH patients in a large multicenter international cohort. We found an improvement in clinical factors for PAH in SSc-PAH patients when treated with macitentan in the vast majority of the patients."

Cardiovascular • Immunology • Pulmonary Arterial Hypertension • Respiratory Diseases • Scleroderma • Systemic Sclerosis

Macitentan vs Standard of Care in Pediatric Pulmonary Arterial Hypertension (TOMORROW): A Randomized Clinical Trial. (PubMed, J Pediatr) - "TOMORROW was a novel study assessing PK and the long-term efficacy and safety of macitentan vs SoC in pediatric PAH. The results confirm the adequacy of the macitentan dosing in this population and provided signals of potential benefit of macitentan over SoC for children with PAH."

Clinical • Journal • Cardiovascular • Hypertension • Pediatrics • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

Overall Patient Characteristics from UNISUS, a Phase 3 Superiority Study Comparing Macitentan 75 mg vs Macitentan 10 mg in Patients with Pulmonary Arterial Hypertension (PAH) (ISHLT 2026) - P3 | "Most (61.4%) had WHO FC II symptoms; 37.8% had FC III symptoms. At screening, 26.4% were receiving 1 PAH therapy, 41.9% 2 therapies and 26.3% ≥3 therapies.Conclusion The UNISUS study will provide robust evidence on the potential to optimize the foundational endothelin pathway with macitentan 75 mg across a broad PAH patient population."

Clinical • Head-to-Head • P3 data • Cardiovascular • Heart Failure • Pulmonary Arterial Hypertension • Respiratory Diseases

Sotatercept for Right Ventricular Failure Following Heart Transplantation in a Patient with Elevated Pulmonary Vascular Resistance: A Case Report (ISHLT 2026) - "She was subsequently started on macitentan 10 mg daily and tadalafil 40 mg daily, resulting in symptomatic improvement and reduction of PVR to 2 WU...Initiation of sildenafil had minimal hemodynamic effect and was compounded by worsening peripheral vasodilation; Macitentan was also resumed...The therapy was well-tolerated and led to clinical and hemodynamic improvement. Future studies need to be conducted to understand the role Sotatercept may represent as a promising option in managing pulmonary vascular disease in the post-transplant setting."

Case report • Clinical • Cardiomyopathy • Cardiovascular • Infectious Disease • Nephrology • Pulmonary Arterial Hypertension • Renal Disease • Respiratory Diseases • Transplantation

Co-Spray-Dried Macitentan-Tadalafil with Leucine Microparticles for Inhalable Delivery in Pulmonary Arterial Hypertension. (PubMed, Pharmaceutics) - " Suspension-based spray drying yielded MAC-TAD composite formulations with improved uniformity and aerosol performance. The optimized 2:8 formulation containing 25% L-leucine demonstrated the most efficient pulmonary deposition, supporting its potential as an inhaled combination therapy for the treatment of PAH."

Journal • Cardiovascular • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

Endothelin-1 in the failing Fontan: pathobiology, precision therapeutics, and future trial design. (PubMed, Front Pediatr) - "Trials of endothelin-receptor antagonists (bosentan, ambrisentan, macitentan) demonstrate reassuring safety and suggest benefit when outcomes emphasize ventilatory efficiency or hepatic endpoints rather than peak oxygen consumption, which is physiologically constrained in Fontan physiology. Given the mixed results of existing trials, a framework is outlined that stratifies Fontan patients into pulmonary-inefficiency, congestive-hepatic, lymphatic, and arrhythmia-dominant phenotypes, using co-primary endpoints such as VE/VCO2 slope, elastography, and biomarker panels. By linking ET-1 biology to pragmatic trial design, this approach emphasizes targeted strategies that may stabilize the circulation, extend transplant candidacy, and improve long-term outcomes."

Journal • Review • Cardiovascular • Heart Failure • Hepatology • Hypertension • Transplantation • EDN1 • RHOA

SMALL ATRIAL SEPTAL DEFECT IN PULMONARY HYPERTENSION: COINCIDENT OR ANTECEDENT? (WRMC 2026) - "The patient was placed on a combination of pulmonary vasodilators which include Macitentan (endothelial receptor antagonist), selexipag (prostacyclin receptor agonist), and tadalafil (phosphodiesterase inhibitor). Figure 1B (Right): The area marked by the circle indicates the shunting of contrast through the atrial septal defect conducted during the bubble study. Right atrium (RA), right ventricle (RV), left atrium (LA), left ventricle (LV) have been labeled."

Autism Spectrum Disorder • Cardiovascular • Developmental Disorders • Epilepsy • Genetic Disorders • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

A study on the accessibility and utilisation of targeted drugs for pulmonary arterial hypertension in China. (PubMed, Front Pharmacol) - "Among all drugs, treprostinil had the highest availability (56.1% across hospitals), while newer drugs such as selexipag had very low availability (3,700 CNY)...Drug accessibility exhibited significant structural imbalances, with some drugs being "affordable but hard to obtain" (e.g., riociguat) and others "highly burdensome and poorly accessible" (e.g., treprostinil). The findings demonstrate significant improvements in the affordability and availability of PAH-targeted therapies over the study period; however, notable inequalities persist in accessibility improvements across urban and rural areas and income groups. Future policies should be tailored to address specific accessibility challenges for different drug categories and focus on overcoming medication access barriers for low-income rural populations to foster health equity."

Journal • Cardiovascular • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

Case Report: Immune checkpoint inhibitor-associated pulmonary hypertension. (PubMed, Front Cardiovasc Med) - "We report a case of a 65-year-old male who developed severe pulmonary arterial hypertension (PAH) following treatment with the programmed cell death protein 1 inhibitor tislelizumab. Following the initiation of a triple combination targeted therapy for PAH comprising macitentan, riociguat, and treprostinil, the patient's condition improved significantly...To date, no specific diagnostic or treatment guidelines exist for this condition due to its rarity. Therefore, there is an urgent need for more case reports, shared experiences, and clinical research to assist clinicians in identifying optimal strategies for the diagnosis and management of this complication."

Checkpoint inhibition • Journal • Cardiovascular • Gastrointestinal Disorder • Hypertension • Oncology • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

MAC-NOCA: Efficacy and Mechanisms of Macitentan for Non-Coronary Obstructive Angina (clinicaltrials.gov) - P1 | N=40 | Recruiting | Sponsor: China-Japan Friendship Hospital

New P1 trial • Cardiovascular

Real-world observational study on pulmonary arterial hypertension: Italian cohort treated with macitentan and/or selexipag as a part of a combination treatment (INSPECTIO). (PubMed, Vascul Pharmacol) - "The INSPECTIO study supports the effectiveness of guideline-directed therapy and regular risk assessment to optimize treatment strategies in PAH. The increase in non-invasive low-risk criteria suggests a stabilization of disease over 12 months."

Journal • Observational data • Real-world evidence • Cardiovascular • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

Macitentan and phosphodiesterase-5 inhibitor alone or in combination in newly diagnosed pulmonary arterial hypertension: a pooled analysis. (PubMed, JHLT Open) - "This large, pooled analysis suggests an observed statistical association indicating a potential survival benefit for early macitentan+PDE5i versus either monotherapy in newly diagnosed PAH."

Journal • Retrospective data • Cardiovascular • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

Liver Transplantation for a Patient With Hemophilia and HIV/HCV Coinfection Complicated by Pulmonary Hypertension. (PubMed, Hepatol Res) - "Preoperative evaluation revealed pulmonary arterial hypertension, which improved with sildenafil citrate, macitentan, and home oxygen therapy. The patient was discharged on postoperative day 51 with normal liver function and good overall condition. This case underscores the importance of multidisciplinary collaboration and careful perioperative planning in achieving successful outcomes in liver transplantation for patients with complex comorbidities such as hemophilia, HIV/HCV coinfection, and pulmonary hypertension."

Journal • Cardiovascular • Hematological Disorders • Hemophilia • Hemophilia B • Hepatitis C • Human Immunodeficiency Virus • Hypertension • Infectious Disease • Pulmonary Arterial Hypertension • Pulmonary Disease • Rare Diseases • Respiratory Diseases • Transplantation

A Study to Assess Whether Macitentan Delays Disease Progression in Children With Pulmonary Arterial Hypertension (PAH) (clinicaltrials.gov) - P3 | N=165 | Completed | Sponsor: Actelion | Active, not recruiting ➔ Completed

Trial completion • Cardiovascular • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

A patient-derived CRISPR platform reveals selective dependencies in Acute Myeloid Leukemia (ASH 2025) - "Our results indicate that EDNRAknockout inhibits AML cell proliferation and growth, highlighting its potential as a therapeutic target.Furthermore, EDNRA is overexpressed in AML compared to normal cells, and since FDA approved EDNRAinhibitors such as Macitentan, Bosentan, Ambrisentan, and Clazosentan are already being used to treatpulmonary arterial hypertension, this presents a promising opportunity to evaluate these inhibitors aspotential chemotherapy-sensitizing agents for high-risk AML.SOD1 plays a critical role in eliminating toxicradicals generated within biological systems and has been associated with poor outcomes in AML. This study demonstrates the establishment of a scalable platform for CRISPR screening inprimary AML cells for identification of more conserved vulnerabilities that may be exploitedtherapeutically, with EDNRA as a potential target. Ongoing work includes validating key targets with thegoal of advancing therapeutic strategies. Future studies will..."

Clinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Pulmonary Arterial Hypertension • Respiratory Diseases • EDNRA • HOXA9 • MEIS1 • PPM1D • SUZ12