Winrevair (sotatercept-csrk) / BMS, Merck (MSD) - LARVOL DELTA

Merck Receives Positive EU CHMP Opinion for Expanded Use of WINREVAIR (sotatercept) in Adults with Pulmonary Arterial Hypertension (PAH, WHO Group 1 Pulmonary Hypertension) (Businesswire) - "The CHMP recommendation will now be reviewed by the European Commission (EC) for amending the marketing authorization in the EU, Iceland, Liechtenstein and Norway, and a final decision is expected in the first quarter of 2026....The CHMP recommendation is based on data from the Phase 3 ZENITH trial..."

CHMP • EMA approval • Immunology • Pulmonary Arterial Hypertension

Sotatercept: from clinical trials to real world data & pearls from practice (PVRI 2026) - No abstract available

Clinical • Real-world • Real-world evidence

Vascular remodeling effects: how else does sotatercept work? (PVRI 2026) - No abstract available

SESSION 1: Sotatercept: from clinical trials to emerging insights (PVRI 2026) - No abstract available

Clinical

Beyond sotatercept, what is the future of TGFb/activin signaling in PAH? (PVRI 2026) - No abstract available

Sotatercept impairs right ventricular function: insights from multi-center preclinical studies (PVRI 2026) - No abstract available

Preclinical

SIRIUS - Initial Combination Therapy With an Endothelin Receptor Antagonist, a Phosphodiesterase-5 Inhibitor and Sotatercept in Patients With Newly Diagnosed Pulmonary Arterial Hypertension (clinicaltrials.gov) - P2 | N=25 | Not yet recruiting | Sponsor: Philipps University Marburg

New P2 trial • Cardiovascular • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

A Clinical Study of Sotatercept (MK-7962) in People With Pulmonary Arterial Hypertension (MK-7962-031/LIGHTRAY EXTENSION) (clinicaltrials.gov) - P2 | N=130 | Active, not recruiting | Sponsor: Merck Sharp & Dohme LLC | Recruiting ➔ Active, not recruiting | Trial completion date: Sep 2027 ➔ Jun 2028 | Trial primary completion date: Sep 2027 ➔ Jun 2028

Enrollment closed • Trial completion date • Trial primary completion date • Cardiovascular • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

LIGHTRAY: A Clinical Study of Sotatercept (MK-7962) in People With Pulmonary Arterial Hypertension (PAH) (MK-7962-024) (clinicaltrials.gov) - P2 | N=164 | Completed | Sponsor: Merck Sharp & Dohme LLC | Active, not recruiting ➔ Completed

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

SOTERIA: A Clinical Study of Sotatercept (MK-7962) in People With Pulmonary Arterial Hypertension (MK-7962-038) (clinicaltrials.gov) - P3 | N=815 | Recruiting | Sponsor: Merck Sharp & Dohme LLC | Not yet recruiting ➔ Recruiting

Enrollment open • Cardiovascular • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

Antiproliferative Therapies in Pulmonary Arterial Hypertension. (PubMed, Expert Opin Pharmacother) - "Targeting these pathways, including BMPR2 restoration, TGF-β inhibition, and tyrosine kinase blockade, has shown encouraging results beyond the vasodilator-focused standard of care. These innovations may reshape PAH management by improving outcomes, and potentially altering disease progression."

Journal • Review • Cardiovascular • Hypertension • Oncology • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • TGFB1

Progressive Pericardial Effusions (PEF) in Patients With Pulmonary Arterial Hypertension (PAH) Taking Sotatercept-Association With Pre-Existing Pericardial Effusion. (PubMed, Pulm Circ) - "Sotatercept was not initially reported as associated with the development or progression of PEF. We describe PAH patients taking sotatercept who were found to have new or worsening PEF and examine associated comorbidities."

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

Sotatercept for pulmonary arterial hypertension on background therapy: a systematic review and meta-analysis of randomized controlled trials. (PubMed, Proc (Bayl Univ Med Cent)) - "Overall adverse events were similar between groups (RR: 1.01, P = 0.65), but class-related events such as bleeding and hematologic abnormalities were more frequent. Sotatercept significantly improves clinical outcomes in PAH but requires close monitoring for bleeding and hematologic adverse events."

Journal • Retrospective data • Review • Cardiovascular • Hematological Disorders • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

StratosPHere 1 study – a novel BMP target engagement biomarker panel for use in clinical trials demonstrates sotatercept alters gene expression in PAH (BTS WM 2025) - "We present discovery and international replication cohorts for the transcriptomic BMPR-II signaling signatures and derive a composite transcriptomic biomarker panel that is repeatable, reproducible, longitudinally stable and expressed in correlated gene modules in PAH which associate with clinical outcomes, most notably mortality. The assay performance characteristics of the biomarker panel make it feasible for early phase, target engagement clinical trials and we have utilised it in a pilot study of sotatercept-treated patients that suggests the therapy does not mechanistically rebalance/increase BMPR-II pathway signaling, but rather shows a reduction, likely due to depletion of circulating BMP9 and BMP10."

Biomarker • Clinical • Cardiovascular • Pulmonary Arterial Hypertension • Respiratory Diseases

Sotatercept is Associated with Improved Lung Function in Sarcoidosis-Associated Pulmonary Hypertension. (PubMed, medRxiv) - "Seven patients (78%) had stable or decreasing background immunosuppression. In patients with sarcoidosis-associated PH, sotatercept was associated with improvement in lung function, and in particular, markers of small airways disease."

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

Sotatercept Improves Small Airway Disease and Hyperinflation in Patients with Pulmonary Hypertension. (PubMed, medRxiv) - "There was no overall change in TLC or FRC. In a real-world cohort of patients with severe precapillary PH from a variety of causes, sotatercept was associated with improvements in markers of SAD and hyperinflation."

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

Merck Canada and the pan-Canadian Pharmaceutical Alliance (pCPA) successfully complete negotiations for WINREVAIR (sotatercept) (Canada Newswire) - "WINREVAIR is indicated in combination with standard pulmonary arterial hypertension (PAH) therapy, for the treatment of adults with World Health Organization [WHO] Group 1 PAH and Functional Class (FC) II or III....The next step involves provincial and territorial governments, and federal drug programs implementing equitable reimbursement to ensure appropriate access to WINREVAIR based on the established patient eligibility criteria from our Health Technology Assessment (HTA) bodies."

Reimbursement • Pulmonary Arterial Hypertension

Odyssey: A Phase 2 Open-Label Study of Momelotinib in Combination with Luspatercept in Patients with Transfusion-Dependent Myelofibrosis (ASH 2024) - P2 | "Patients may be JAK inhibitor naive (cohort 1; approximate n=28) or experienced (cohort 2; approximate n=28); previous or current ruxolitinib or fedratinib use is permitted in cohort 2, and all other MF-directed therapy must be discontinued ≥28 days before enrollment in both cohorts. Exclusion criteria include platelet counts of <50×109/L; prior treatment with any ACVR1 inhibitor, luspatercept, or sotatercept; history of gastrointestinal disease likely to alter absorption of momelotinib; clinically significant anemia due to mechanisms other than MF; uncontrolled infections, bleeding, acute/chronic liver disease, or hypertension; stroke or other thromboembolic events in the prior 6 months; and grade ≥2 peripheral neuropathy...Exploratory endpoints include assessments of symptoms and quality of life, additional measures of anemia-related benefit and pharmacokinetics, spleen size reduction, and peripheral blood-based biomarkers including iron metabolism and..."

Clinical • Combination therapy • P2 data • Anemia • Beta-Thalassemia • Cardiovascular • Gastroenterology • Gastrointestinal Disorder • Genetic Disorders • Hematological Disorders • Hematological Malignancies • Hepatology • Hypertension • Infectious Disease • Inflammation • Myelodysplastic Syndrome • Myelofibrosis • Oncology • ACVR1 • JAK1 • TGFB1

Merck’s WINREVAIR (sotatercept-csrk) Met Primary Endpoint in Phase 2 CADENCE Study in Adults With Combined Post- and Precapillary Pulmonary Hypertension (CpcPH) due to Heart Failure With Preserved Ejection Fraction (HFpEF) (Merck (MSD) Press Release) - "CADENCE met its primary endpoint, showing a statistically significant and clinically meaningful reduction in pulmonary vascular resistance (PVR) from baseline at 24 weeks compared to placebo. Based on a preliminary assessment, the safety profile observed in the CADENCE study was generally consistent with the known safety profile for WINREVAIR....The company is planning to present these results at a future scientific congress and intends to proceed with Phase 3 development."

P2 data • Pulmonary Arterial Hypertension

American Lung Association Pulmonary Hypertension Roundtable: Executive Summary. (PubMed, Pulm Circ) - "3) Provide guidance for the incorporation of the recently approved drug, sotatercept into current guidelines...The role of screening for PH in high-risk populations and the use of risk scores for disease stratification are discussed. Finally, treatment algorithms for managing pulmonary arterial hypertension, PH associated with lung disease, and chronic thromboembolic pulmonary hypertension are presented."

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

Acute Hemodynamic Effects of Sotatercept in Pulmonary Arterial Hypertension (AHA 2025) - P | "Our findings provide the first indication of an acute pulmonary vasodilatory effect of sotatercept. Sotatercept may rapidly unload the RV but does not influence RV–PA coupling acutely. Clinically, sotatercept could be beneficial for immediate RV unloading in acute settings."

Late-breaking abstract • Cardiovascular • Pulmonary Arterial Hypertension • 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

Biased small molecule RXFP1 agonists ameliorate experimental pulmonary hypertension and RV hypertrophy (AHA 2025) - "Serum and PDGF-BB-induced migration of PASMC were inhibited by RLN2, ML290 and derivatives. Humanized RXFP1 knock-in (hRXFP1-KI) mice subjected to SU5416 and hypoxia (FiO2=0.1) for three weeks and treated with ML290, TRND8394, AZD5462 (10 mg/kg/d p.o.), or ACTRIIA-Fc (a.k.a., sotatercept, 2.2 mg/kg/twice weekly i.p.) had comparable improvements in right ventricular systolic pressure (RVSP) vs. disease controls, while treatment with biased compounds ML290 and TRND8394, and ACTRIIA-Fc elicited potent decreases in RV hypertrophy (RV/LV+S).ConclusionSmall molecule RXFP1 agonists with biased GPCR signaling may elicit more potent effects in experimental PH upon right ventricular hypertrophy than non-biased RXFP1 agonists and represent a promising therapeutic strategy for cardiopulmonary disease."

Cardiovascular • Congestive Heart Failure • Heart Failure • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • ACVR2A • CALD

HS235, a Novel Activin Signaling Inhibitor, is Highly Efficacious in Preclinical Models of Pulmonary Hypertension and Heart Failure (AHA 2025) - "Briefly, mice underwent TAC surgery, recovered for 2 weeks, and were then treated with vehicle, HS235, or wild-type ActRIIA-Fc (a sotatercept surrogate) for 4 weeks. HS235 improved PH, HF, body composition and exercise tolerance in in vivo models. These results demonstrate the differentiated therapeutic profile of HS235 and support its further development as a novel treatment of cardiopulmonary and cardiometabolic diseases."

Preclinical • Cardiovascular • Congestive Heart Failure • Genetic Disorders • Heart Failure • Metabolic Disorders • Obesity • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • ACVR2A

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