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

Long-Term Safety and Exposure-Adjusted Incidence Rates of Adverse Events From Pooled Sotatercept Studies (PULSAR, SPECTRA, STELLAR, and SOTERIA) (ATS 2025) - P2, P3 | "The TAR-EAIRs of TEAEs, including serious bleeding events, were generally stable over time. In conjunction with preliminary data demonstrating durability of efficacy, these exposure-adjusted safety data from a pooled dataset support that the positive benefit-risk profile of sotatercept is maintained with longer-term treatment."

Adverse events • Clinical • Late-breaking abstract • Cardiovascular • Hematological Disorders • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • Thrombocytopenia

Early Outcomes of Sotatercept in Pulmonary Arterial Hypertension (ATS 2025) - "Our study showed improvements in PAH severity with minimal side effects, consistent with published data. This study includes patients that were excluded in phase 3 clinical trials including those with unrepaired congenital heart disease, active methamphetamine use, and HIV. This is to our knowledge the first study demonstrating significant improvement in RVFWS after sotatercept."

Cardiovascular • Heart Failure • Human Immunodeficiency Virus • Immunology • Infectious Disease • Pulmonary Arterial Hypertension • Respiratory Diseases • Rheumatology • Scleroderma • Systemic Sclerosis

Transcriptomic Analysis of Endothelial and Smooth Muscle Cells Isolated From Patients With Pulmonary Arterial Hypertension May Aid in Understanding Responses to Therapy (ATS 2025) - "However, sotatercept, a recently approved drug for PAH, uniquely targets the activin/BMP pathway, regressing disease specific abnormalities... Understanding the cellular phenotypic variation in PAH is essential to test individual cellular responses to PAH specific treatments and move the field closer to precision medicine. CECs isolated from PAH patients shared similarities with PAH-PAEC and PAH-SMC, offering valuable insights into patient-specific molecular changes, supporting a personalized approach to PAH treatment."

Clinical • Omic analysis • Cardiovascular • Congestive Heart Failure • Heart Failure • Pulmonary Arterial Hypertension • Respiratory Diseases • ACVRL1 • IL7R • PDE5A • PTGER4 • SMURF1 • TBX3

Sotatercept Improves Hypoxia and Clinical Status in Patients With Pulmonary Venous Occlusive Disease (ATS 2025) - "CONCLUSION Sotatercept appears promising as an effective and well-tolerated therapy in patients with PVOD with prominent improvement in hypoxia along and with improvements in functional status, RV parameters, and oxygen needs. Sotatercept should be considered early as a treatment option for patients with PVOD."

Clinical • Cardiovascular • Hematological Disorders • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • Thrombocytopenia

Thrombocytopenia Caused by Treprostinil (ATS 2025) - "Besides recently approved Sotatercept, historically, there have been three major classes of drugs used for medical management: endothelin antagonists, phosphodiesterase 5 inhibitors, and prostacyclin analogs...Patient was diagnosed with severe PAH, WHO (World Health Organization) functional class IV and was on Sildenalfil, Macitentan and subcutaneous Treprostinil that were started few months prior...Patient failed to respond to a trial of dexamethasone, however the platelet count improved significantly with Intravenous immunoglobulin (IVIG)...Therefore, careful down-titration of Treprostinil was done with simultaneous treatment with IVIG initially followed by rituximab. In summary, this case will add to the prevailing literature regarding PAH treatment and severe thrombocytopenia."

Cardiovascular • Fatigue • Gastroenterology • Hematological Disorders • Hematological Malignancies • Multiple Myeloma • Myelodysplastic Syndrome • Oncology • Plasmacytoma • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • Rheumatology • Thrombocytopenia

Pulmonary Arteriovenous Malformations in BMPR2-Associated Pulmonary Arterial Hypertension (ATS 2025) - "At the time of her relocation, she was on triple oral therapy with riociguat, selexipag, and macitentan with low-risk by REVEAL score and mildly decreased right ventricular function on echocardiography. Whether sotatercept in these patients can worsen pre-existing AVMs is unknown. Figure 1."

Cardiovascular • CNS Disorders • Heart Failure • Hematological Disorders • Myasthenia Gravis • Pulmonary Arterial Hypertension • Respiratory Diseases • ACVR2A

A Challenging Diagnosis: When to Suspect Pulmonary Veno-occlusive Disease (ATS 2025) - "Tadalafil was initially started followed by macitentan, which were associated with worsening hypoxemia and dyspnea...She was discharged with plans to continue low dose outpatient epoprostenol and start sotatercept...Management is challenging given ineffective or potentially harmful responses to PAH-directed therapies, though some do respond to a variable extent. As suggested here, close supervision during epoprostenol infusion adds to the limited body of evidence supporting such endeavors when initiating vasodilatory therapies in patients with suspected PVOD."

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

Thrombocytopenia Associated With Epoprostenol and Treprostinil Alone and in Combination With Sotatercept (ATS 2025) - "In the pivotal trials for subcutaneous treprostinil and intravenous epoprostenol, clinically significant changes in hematologic variables were not observed; however, laboratory values were not included in the publications. When PPs were combined with sotatercept, thrombocytopenia incidence increased; however, the specific prostacyclin, and dose were unavailable (Hoeper, 2023).ConclusionEpoprostenol may be more likely to cause thrombocytopenia, and amongst patients receiving epoprostenol and experiencing thrombocytopenia, transitioning to parenteral treprostinil may be considered. However, additional higher quality data on rates of thrombocytopenia associated with PAH medication use, in light of sotatercept, is warranted."

Combination therapy • Cardiovascular • Hematological Disorders • Pulmonary Arterial Hypertension • Respiratory Diseases • Thrombocytopenia

Sotatercept Super-responder: Rapid Right Ventricular Remodeling in Systemic Sclerosis Associated Pulmonary Arterial Hypertension (ATS 2025) - "She was weaned off treprostinil with significant improvement in function and was able to return to work. As sotatercept becomes adopted into the treatment algorithm for PAH, understanding "super responder" phenotypes is important as they may reveal targetable mechanisms that decrease therapy burden and side effects in certain disease populations. This case demonstrates the therapeutic impact of sotatercept, the first in a new class of drugs PAH treatment."

Cardiovascular • Heart Failure • Immunology • Inflammation • Musculoskeletal Pain • Pain • Pulmonary Arterial Hypertension • Respiratory Diseases • Rheumatology • Scleroderma • Systemic Sclerosis

The Phourth Pathway in PAH: Experience in the "Underserved" Central Valley of California (ATS 2025) - "Sotatercept (SOT) is the new activin inhibitor recently added as the fourth pathway...Case 1: A 45-year-old African-American female with WHO group 1 CTD-PAH reported worsening symptoms despite triple therapy (Parenteral prostacyclin therapy (PPT) + Endothelin receptor agonist (ERA) + Tadalafil (TAD)...Case 3: A 53-year-old Hispanic male with IPAH was on Triple combo treatment (Oral prostacyclin + ERA + Riociguat (Rio))... These cases illustrate favorable responses to SOT in patients with progressive PAH. Often, Symptom improvement was perceived as soon as after 1st dose. Of 4 patients, SOT had to be stopped in 1 patient due to significant Thrombocytopenia despite favorable clinical response."

Cardiovascular • Congestive Heart Failure • Heart Failure • Hematological Disorders • Immunology • Inflammatory Arthritis • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • Sjogren's Syndrome • Thrombocytopenia

Hemodynamic and Echocardiographic Outcomes of Sotatercept in Patients With Group 1 Pulmonary Arterial Hypertension (PAH) (ATS 2025) - "Sotatercept demonstrates favorable hemodynamic and echocardiographic effects, including improvements in RVSP, in patients with Group 1 PAH after 5 doses, suggesting its potential role as an adjunctive treatment in this population. These findings provide valuable insights into Sotatercept's mechanism of action and support its consideration for integration into PAH management guidelines."

Clinical • Cardiovascular • Congestive Heart Failure • Heart Failure • Pulmonary Arterial Hypertension • Respiratory Diseases

Rapid Hemodynamic Improvement With Sotatercept in Pulmonary Arterial Hypertension Patients With Cardiomems Implant (ATS 2025) - "Long term sustained response remains unclear but warrants further exploration. Further research into the role of sotatercept in the treatment algorithm for this chronic and progressive disease should be pursued."

Clinical • Cardiovascular • Congestive Heart Failure • Heart Failure • Pulmonary Arterial Hypertension • Respiratory Diseases

Gastrointestinal Bleeding Associated With Activin Signaling Inhibitor (Sotatercept) Use in a Patient With Systemic Sclerosis Associated Pulmonary Arterial Hypertension (PAH), Walking a Thin Line? (ATS 2025) - "With the increasing use of this new therapy in patients with SSc-PAH, it is important to understand the risk and the management of GI bleeding in this challenging population. In this case report, we describe our experience in managing telangiectasia associated GI bleeding in a patient with SSc-PAH."

Clinical • Anemia • Cardiovascular • CNS Disorders • Fatigue • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Immunology • Inflammation • Pulmonary Arterial Hypertension • Respiratory Diseases • Scleroderma • Systemic Sclerosis • TGFB1

Overall Survival of Patients on Sotatercept: An Analysis of STELLAR and SOTERIA Trials (ATS 2025) - P3 | "Conclusions In this analysis of two Phase 3 trials, sotatercept was shown to significantly reduce the risk of death compared to placebo. Future analyses of longer-term sotatercept exposure are warranted once all on-going trials are completed and unblinded."

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

The Cibotercept Analog RKER-012 Did Not Inhibit BMP/ALK1-dependent Retinal Neovascularization (ATS 2025) - P2 | "Sotatercept, an activin receptor type IIA ligand trap, is an approved drug for PAH but has been associated with an increased risk of bleeding1. RKER-012 did not alter retinal vessel growth in neonatal mice, a process largely dependent on BMP/ALK1 activation2. This, along with the observed lack of impact on erythrocytosis in preclinical studies and a Phase 1 trial of cibotercept in healthy volunteers, suggests that cibotercept can potentially avoid or reduce bleeding risk. These preclinical findings further support rationale for the ongoing Phase 2 trial of cibotercept in patients with PAH (NCT05975905)."

Age-related Macular Degeneration • Cardiovascular • Hematological Disorders • Pulmonary Arterial Hypertension • Respiratory Diseases • ACVR2A • ALK1

Development of New Intrapulmonary Shunts in Pulmonary Arterial Hypertension Treated with Sotatercept. (PubMed, Am J Respir Crit Care Med) - No abstract available

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

Simplifying Sotatercept in Pulmonary Arterial Hypertension: Genetic Context Meets Treatment-Response. (PubMed, Am J Respir Crit Care Med) - No abstract available

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

Severe Hypoxemia and Pulmonary Capillary Dilatations in PAH Patients Treated with Sotatercept. (PubMed, Am J Respir Crit Care Med) - No abstract available

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

HARMONIZE: Extension Study of Sotatercept in People With Pulmonary Hypertension (MK-7962-023) (clinicaltrials.gov) - P2 | N=130 | Recruiting | Sponsor: Merck Sharp & Dohme LLC | Not yet recruiting ➔ Recruiting

Enrollment open • Cardiovascular • Congestive Heart Failure • Heart Failure • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

SOTERIA: A Long-term Follow-up Study of Sotatercept for PAH Treatment (MK-7962-004/A011-12) (clinicaltrials.gov) - P3 | N=700 | Active, not recruiting | Sponsor: Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USA | Recruiting ➔ Active, not recruiting

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

Sotatercept as add-on therapy for advanced PAH. (PubMed, Nat Rev Cardiol) - No abstract available

Journal

Withdrawal of prostacyclin pathway therapies after initiation of sotatercept treatment in patients with pulmonary arterial hypertension. (PubMed, Eur Respir J) - No abstract available

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

Merck Announces First-Quarter 2025 Financial Results (Merck (MSD) Press Release) - "KEYTRUDA Sales Grew 4% to $7.2 Billion; Excluding the Impact of Foreign Exchange, Sales Grew 6%. WINREVAIR Sales Were $280 Million. GARDASIL/GARDASIL 9 Sales Declined 41% to $1.3 Billion; Excluding the Impact of Foreign Exchange, Sales Declined 40%."

MSI-H • Sales • Biliary Tract Cancer • Cervical Cancer • Cholangiocarcinoma • Endometrial Adenocarcinoma • Head and Neck Cancer • HER2 Negative Breast Cancer • Melanoma • Microsatellite Instability • Neuroendocrine Tumor • Non Small Cell Lung Cancer • Pancreatic Cancer • Pulmonary Arterial Hypertension

PAH Exercise Study (clinicaltrials.gov) - P3 | N=10 | Recruiting | Sponsor: University of Washington

New P3 trial • Cardiovascular • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

Real-world sotatercept elegibility: analysis from FOCUS-PAH registry (HEART FAILURE 2025) - No abstract available

Clinical • Real-world • Real-world evidence • Cardiovascular • Hypertension • Pulmonary Embolism