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

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

Persistent Pulmonary Hypertension in Corrected Congenital Left Circumflex Artery to Coronary Sinus Fistula: A Case Report and Literature Review. (PubMed, Case Rep Cardiol) - "Postoperatively, the patient remained symptomatic, with elevated pulmonary arterial pressure persisting, prompting the initiation of triple therapy comprising macitentan, selexipag, and sildenafil. The case illustrates a rare case of persistent PHTN in a corrected LCx-CS fistula. Thorough follow-up, early diagnosis, and timely interventions, complemented by pharmacotherapy when necessary, are essential in managing these complex clinical scenarios."

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

Selection of Endothelin Receptor Antagonists in the Treatment of Pulmonary Arterial Hypertension: A Comprehensive Narrative Review. (PubMed, Adv Ther) - "Endothelin receptor antagonists (ERAs) are established treatments for PAH, and three agents-bosentan, ambrisentan, and macitentan-are approved for use in adults in the USA. It also discusses the differing physicochemical and pharmacokinetic properties of each ERA and how these unique characteristics influence their receptor binding and kinetics, mechanisms of action, therapeutic effects, dosing frequency, and safety in PAH. In the absence of head-to-head clinical trials assessing their comparative efficacy and safety, it is important to understand both the similarities and the distinguishing characteristics of the three ERAs approved in PAH, to inform individualized treatment selection."

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

Acute Decompensated Heart Failure in a Woman With Eisenmenger Syndrome: A Case Report. (PubMed, Cureus) - "It emphasizes the importance of maintaining a high index of suspicion in the presence of chronic hypoxia and abnormal hematologic parameters. We discuss the role of echocardiography and adjunctive imaging in diagnosis, review the pathophysiologic mechanisms underlying ES, and outline current therapeutic strategies, including the use of endothelin receptor antagonists in the management of pulmonary arterial hypertension (PAH)."

Journal • Cardiovascular • Congestive Heart Failure • Heart Failure • Hematological Disorders • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

The Involvement of the Peptidergic Systems in Breast Cancer Development. (PubMed, Cancers (Basel)) - "Breast cancer cells overexpress peptide receptors; at the same time they are known to interact with peptides that (a) exert an oncogenic action (adrenomedullin 2, endothelin, gastrin-releasing peptide, neurokinin A, neuromedin, neuropeptide Y, neurotensin, substance P, vasoactive intestinal peptide), (b) exert an anticancer action (angiotensin (1-7), ghrelin, peptide YY) or (c) exert dual oncogenic and anticancer effects (adrenomedullin, angiotensin II, bradykinin, corticotropin-releasing factor, β-endorphin, glucagon-like peptide 1, gonadotropin-releasing hormone, kisspeptin, methionine-enkephalin, oxytocin)...Future lines of research are suggested in breast cancer using promising anti-breast-cancer peptide receptor antagonists (HOE-140, exendin (9-39), bosentan, macitentan, PD168,368, CGP71,683A, SR48,692, aprepitant) or agonists (FR190,997, semaglutide, exendin 4, goserelin) mentioned in this review...Taken together, the available data highlight the enormous promise..."

Journal • Review • Breast Cancer • Oncology • Solid Tumor • GRP-10

Results of the MACiTEPH study of macitentan for the treatment of inoperable or persistent/recurrent chronic thromboembolic pulmonary hypertension. (PubMed, J Heart Lung Transplant) - P3 | "MACiTEPH was discontinued for futility, as no treatment effect on 6MWD (primary endpoint) was observed. Despite the higher discontinuation rate in the macitentan 75 mg group, no unexpected safety signals were observed in CTEPH patients."

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

Characteristics, Treatment Patterns and Outcomes of Patients with Pulmonary Arterial Hypertension by Race and Ethnicity Using Real-World Data from the Combined OPUS/OrPHeUS Studies. (PubMed, Adv Ther) - P | "OPUS/OrPHeUS provides real-world insights into racial/ethnic minority groups receiving macitentan and other PAH-specific treatments in the USA. These data on treatment patterns and outcomes could help inform treatment decisions in the reported minority groups."

Journal • Real-world evidence • Cardiovascular • Heart Failure • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • Rheumatology

Macitentan Plus Tadalafil Single-Tablet Combination Therapy in Chinese Patients With Pulmonary Arterial Hypertension: A Subgroup Analysis of the A DUE Study. (PubMed, Pulm Circ) - P3 | "Our findings support the use of M/T STCT for PAH in China. Trial registration: ClinicalTrials.gov https://clinicaltrials.gov/ NCT03904693 (April 5, 2019)."

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

Sotatercept-Enhanced Quadruple Therapy Reverses Hemodynamic Decline in Severe Systemic Lupus Erythematosus-Associated Pulmonary Arterial Hypertension (AHA 2025) - "Treatment included high-dose corticosteroids, mycophenolate mofetil, rituximab, tadalafil, macitentan, and continuous epoprostenol infusion. This case demonstrates that a proactive, multidisciplinary approach incorporating novel therapies such as sotatercept can reverse the trajectory of life-threatening SLE-PAH. Timely diagnosis, aggressive immunosuppression, and layered vasodilator regimens can restore cardiopulmonary function and delay or avoid transplantation in patients with advanced disease."

Cardiovascular • Glomerulonephritis • Immunology • Inflammatory Arthritis • Lupus • Lupus Nephritis • Nephrology • Pulmonary Arterial Hypertension • Respiratory Diseases • Systemic Lupus Erythematosus

Case report: Successful use of sotatercept to treat pulmonary arterial hypertension in a patient with hereditary hemorrhagic telangiectasia. (PubMed, Respir Med Case Rep) - "Despite long-term treatment with epoprostenol, treprostinil, macitentan, and tadalafil, her condition progressed, leading to evaluation for lung transplantation. This is the first reported case of sotatercept use in HHT-associated PAH, highlighting its potential efficacy but also the need for careful monitoring due to increased bleeding risk. Further studies are required to establish the safety and efficacy of sotatercept in this population."

Journal • Cardiovascular • Heart Failure • Hematological Disorders • Hypertension • Otorhinolaryngology • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • Transplantation • TGFB1

Interactions between Integrin α9β1 and VCAM-1 Promote Neutrophil Hyperactivation and Deep Vein Thrombosis in a Murine Model of Lung Cancer (ASH 2023) - "Virtual screening and cell-free assay identified macitentan as a potent inhibitor of integrin α9-VCAM-1 interactions... Using genetic and pharmacological approaches in combination with transcriptomic and pharmacological studies, we described a previously unknown pathway involving integrin α9 and VCAM-1 in promoting cancer-associated thrombosis. We found that integrin α9-VCAM1 axis is critical for neutrophil hyperactivation, and its pharmacological inhibition significantly reduces DVT severity. The results of this study suggest that neutrophil integrin α9 is a key factor regulating neutrophil hyperactivation and cancer-associated thrombosis."

Preclinical • Cardiovascular • Lung Cancer • Oncology • Solid Tumor • Thrombosis • Venous Thromboembolism • ELANE • MPO • VCAM1

Macitentan in the Treatment of Digital Ulcers in Patients with Systemic Rheumatic Autoimmune Diseases: A National Multicenter Study of 42 Patients. (PubMed, J Clin Med) - "GI and higher ulcer burden predicted diminished treatment response in SSc patients. These results support the use of MACI as a valuable therapeutic option for severe digital vasculopathy in SARDs, although further prospective studies are warranted to confirm these observations."

Clinical • Journal • Cardiovascular • Immunology • Rheumatology • Scleroderma • Systemic Sclerosis

Preferences for pulmonary arterial hypertension (PAH) medications: plain language summary on insights from interviews with patients and doctors in the A DUE phase 3 clinical study. (PubMed, Future Cardiol) - No abstract available

Interview • Journal • P3 data • Cardiovascular • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

Severe Pulmonary Hypertension in a Young Adult with Congenital Diaphragmatic Hernia: A Challenging Case of Multifactorial Developmental Lung Disease. (AHA 2025) - "He developed severe PH requiring extracorporeal membrane oxygenation (ECMO), prostaglandins, and prolonged dual therapy with endothelin receptor antagonists (bosentan, macitentan)...At age 20, clinical deterioration followed the introduction of selexipag, with worsening hypoxemia, increased oxygen requirements, and suspicion of pulmonary vascular disease progression...This case underscores the complex trajectory of PH in survivors of CDH and the risks associated with transitions in pulmonary vasodilator therapy. It highlights the need for long-term multidisciplinary follow-up and raises concerns about late-onset pulmonary vascular deterioration. Novel strategies and biomarkers are needed to better phenotype and risk-stratify this unique patient population.Use of AI tools:No automated editing assistance was used."

Clinical • Cardiovascular • Developmental Disorders • Gastroenterology • Psychiatry • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

DOUBLE TROUBLE: A CASE OF DASATINIB-INDUCED PULMONARY ARTERIAL HYPERTENSION AND RECURRENT CHYLOTHORAX (CHEST 2025) - "She was started on tadalafil, macitentan, and orenitram...Bosutinib was discontinued, and she was started on asciminib, with no further recurrence of effusions... While generally well tolerated, this case highlights rare manifestations of TKI side effects and underscores importance of evaluating pulmonary symptoms that coincide with the initiation of these therapies."

Clinical • Cardiovascular • Chronic Myeloid Leukemia • Congestive Heart Failure • Diabetes • Genetic Disorders • Heart Failure • Hematological Malignancies • Leukemia • Metabolic Disorders • Obesity • Obstructive Sleep Apnea • Pulmonary Arterial Hypertension • Respiratory Diseases • Sleep Disorder • Type 2 Diabetes Mellitus

Schistosomiasis-Induced Cirrhosis With Multifactorial Pulmonary Hypertension: A Case Report (ACG 2025) - "After starting macitentan-sildenafil, repeat RHC showed mPAP 50mmHg, still ineligible for exception points...A PAH specialist classified his condition as multifactorial: WHO Group 1 PAH due to portopulmonary hypertension (POPH), as well as WHO Group 2 PAH from heart failure from poorly controlled diabetes and hypertension.He is symptomatically managed with lactulose, beta blockers, and diuretics...Post treatment it exceeded the threshold and posed a surgical risk, excluding him from transplant eligibility. The case highlights the severe complications of schistosomiasis, the narrow eligibility window on POPH, and complexity in managing such multifactorial disease."

Case report • Clinical • Cardiovascular • Congestive Heart Failure • Diabetes • Fibrosis • Heart Failure • Hepatology • Hypertension • Immunology • Infectious Disease • Inflammation • Metabolic Disorders • Portal Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

Marked improvement in severe pulmonary arterial hypertension following airway infection in a patient with a heterozygous BMP9 nonsense mutation: a case report. (PubMed, Eur Heart J Case Rep) - "Despite receiving combination therapy with macitentan, riociguat, and intravenous epoprostenol, she continued to have severe pulmonary hypertension with suprasystemic pressure [mean pulmonary artery pressure (PAP) = 65 mmHg] for 4 years following treatment initiation. A patient with severe, treatment-resistant pulmonary hypertension exhibiting a dramatic improvement in pulmonary pressure following an AI is exceedingly rare. The present case may provide new insights into the pathophysiology of PAH."

Journal • Cardiovascular • Hypertension • Infectious Disease • Inflammation • Pneumonia • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

A NOVEL CASE OF VEGF-INHIBITOR THERAPY IN PULMONARY ARTERIAL HYPERTENSION DUE TO HEREDITARY HEMORRHAGIC TELANGIECTASIA (CHEST 2025) - "Her PAH was managed with subcutaneous treprostinil, macitentan, furosemide, and spironolactone, with significant symptomatic improvement despite ongoing severe PAH by hemodynamic measurements...Her anemia persisted despite intravenous ferumoxytol 1020 mg 1-2 times per week...This dysregulated BMP signaling pathway is the target of Sotatercept, the newest FDA-approved PAH therapy... The VEGF-inhibitor Bevacizumab has proven clinical benefits in HHT, yet there is no direct evidence supporting its use in PAH. This case demonstrates that Bevacizumab may be used safely in patients with PAH and HHT, and may improve PAH-specific metrics such as PASP, though further studies are needed to confirm its role in PAH."

Clinical • Anemia • Cardiovascular • CNS Disorders • Fatigue • Genetic Disorders • Hematological Disorders • Pulmonary Arterial Hypertension • Respiratory Diseases • ACVR2A • ACVRL1 • ALK1 • TGFB1

SEVERE PULMONARY ARTERIAL HYPERTENSION POSTLOBECTOMY FOR LUNG CANCER (CHEST 2025) - "His prior chemotherapies (paclitaxel, carboplatin, and volrustomig) have not previously been associated with PH, and TTE was normal after drug exposure...He was subsequently started on sildenafil 20 mg three times daily, digoxin 125 mcg daily, and furosemide 20 mg daily...Macitentan was discontinued with improvement in peripheral edema and sildenafil was also subsequently weaned... PH post-MLR is an important contributor to morbidity and mortality. Future research will help better risk stratify those who are at risk of developing severe PH and to understand the impact of early PH therapy initiation on reversal pulmonary vasculopathy."

Cardiovascular • Congestive Heart Failure • Heart Failure • Hypertension • Immunology • Lung Cancer • Oncology • Pulmonary Arterial Hypertension • Respiratory Diseases • Solid Tumor • Squamous Cell Carcinoma

THE IMPACT OF THE HUMAN MONOCLONAL ANTIBODY REGN13335 ON PDGF-B: A POTENTIAL, NOVEL THERAPEUTIC STRATEGY FOR PULMONARY ARTERIAL HYPERTENSION (CHEST 2025) - "Combining REGN13335 with the endothelin receptor antagonist macitentan improved survival compared to vehicle control treatment and macitentan monotherapy in MCT rats. In the bleomycin-induced lung fibrosis model, REGN13335 mitigated RVSP elevation... Neutralizing PDGF-B with REGN13335 reduces PDGF-BB/AB signaling through PDGFR-α and PDGFR-β on vascular support cells and fibroblasts, contributing to remodeling and pulmonary resistance. REGN13335 demonstrated efficacy in mitigating PAH-related endpoints across preclinical models of primary and secondary PAH. CLINICAL IMPLICATIONS: These findings suggest that the PDGF-B antagonist monoclonal antibody REGN13335 may represent a promising therapeutic strategy for PAH treatment, potentially reducing the risk of right heart failure and improving survival in patients with PAH."

Anemia • Cardiovascular • Congestive Heart Failure • Fibrosis • Genetic Disorders • Heart Failure • Hematological Disorders • Immunology • Pulmonary Arterial Hypertension • Respiratory Diseases • Sickle Cell Disease • PDGFRA • PDGFRB

SICKLE CELL DISEASE LEADING TO DEBILITATING PULMONARY ARTERIAL HYPERTENSION (CHEST 2025) - "Managing SCD-associated PH primarily focuses on treating the underlying disease with hydroxyurea or chronic blood exchange transfusions, along with anticoagulation for thromboembolism and treatment of left heart failure in those with post-capillary PH...Given clinical volume overload, she was started on torsemide...Although intended to be started on macitentan (an endothelin receptor antagonist), she returned to the hospital with worsening dyspnea before she could get the medication approved...She then became increasingly hypotensive riociguat was uptitrated, requiring initiation of midodrine as well as downtitration of diuresis... SCD-associated PH carries a high mortality risk with a notable lack of evidence on effective therapy options that demonstrate significantly improved outcomes."

Cardiovascular • Congestive Heart Failure • Genetic Disorders • Heart Failure • Hematological Disorders • Hypotension • Pulmonary Arterial Hypertension • Respiratory Diseases • Sickle Cell Disease

DE-ESCALATION OF THERAPY IN THE SETTING OF SOTATERCEPT IN PULMONARY ARTERIAL HYPERTENSION PATIENTS ON PREVIOUSLY STABLE PARENTERAL PROSTACYCLIN (CHEST 2025) - "CASE PRESENTATION: A 38-year-old female with Ehlers-Danlos and World Health Organization (WHO) group 1 PAH on triple therapy (subcutaneous treprostinil 30 ng/kg/min, macitentan, riociguat) was started on sotatercept...Six minute walk distance (6MWD) improved (460m) as did her functional class (II).A 55-year-old female with methamphetamine-associated PAH on triple therapy (epoprostenol 16.5ng/kg/min, macitentan, riociguat) was started on sotatercept...Epoprostenol was tapered off over 2 days and was transitioned selexipag... These cases highlight the importance of regular follow-up, monitoring, and dose modifications to PAH therapies. Further studies are needed to evaluate the long-term impact of sotatercept and its interactions with other PAH therapies."

Clinical • Cardiovascular • Endocrine Disorders • Infectious Disease • Nephrology • Novel Coronavirus Disease • Pneumonia • Pulmonary Arterial Hypertension • Renal Disease • Respiratory Diseases

Case 1: Syncope as an early warning sign of pulmonary arterial hypertension (PAH) – an interdisciplinary challenge (OGP-OGTC 2025) - "His medical history includes depression and obsessive-compulsive personality disorder, which are being treated with quetiapine and venlafaxine...The patient received dual drug therapy with Adcirca (tadalafil) and Opsumit (macitentan)...Diagnosis: During the inpatient evaluation of a patient with a history of psychiatric illness who was initially largely symptom-free and suffered from recurrent syncope, the cause was diagnosed as severe precapillary pulmonary arterial hypertension. Further investigation into the etiology of PAH, including genetic testing, is currently underway."

Clinical • Cardiovascular • CNS Disorders • Depression • Mental Retardation • Musculoskeletal Diseases • Obsessive-Compulsive Disorder • Orthopedics • Personality Disorder • Psychiatry • Pulmonary Arterial Hypertension • Pulmonary Disease • Pulmonary Embolism • Respiratory Diseases

SEVERE PORTOPULMONARY HYPERTENSION IN A POST-LIVER TRANSPLANT PATIENT LEADING TO ACUTE RESPIRATORY FAILURE (CHEST 2025) - "He was started on intravenous epoprostenol and gradually transitioned to sildenafil and macitentan...(2023)[1] reported successful management of POPH with combined tadalafil and macitentan... Severe POPH following LT presents significant management challenges. Early recognition and aggressive treatment are crucial to improving patient outcomes. This case highlights the importance of routine hemodynamic monitoring and pulmonary screening in liver transplant recipients to ensure timely intervention for evolving pulmonary vascular complications."

Clinical • Atrial Fibrillation • Cardiovascular • Chronic Kidney Disease • Fibrosis • Gastroenterology • Gastrointestinal Disorder • Hepatology • Immunology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Nephrology • Portal Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Pulmonary Embolism • Renal Disease • Respiratory Diseases • Transplantation

EVALUATING THE COMPARATIVE EFFECTIVENESS OF ENDOTHELIN INHIBITORS IN IDIOPATHIC PULMONARY FIBROSIS: A COMPREHENSIVE BAYESIAN NETWORK META-ANALYSIS WITH INTERVENTION RANKING (CHEST 2025) - "This study suggests that bosentan and macitentan are the most effective endothelin inhibitors for managing idiopathic pulmonary fibrosis (IPF) in terms of improving disease progression and lung function, with higher SUCRA values indicating superior efficacy. Ambrisentan showed the least benefit across several outcomes, including FVC and DLCO. CLINICAL IMPLICATIONS: Clinicians may consider bosentan and macitentan as preferred options for managing IPF due their better efficacy profiles, particularly in slowing disease progression and improving lung function."

HEOR • Retrospective data • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases • EDN1