What are the highlights for a clinical trial with Sotatercept (ACE-011)?

From the Guidelines

Sotatercept is not mentioned in the provided evidence, however, luspatercept, a similar drug, has shown promising results in treating myelodysplastic syndromes (MDS) with a 63% erythroid response and 38% RBC transfusion independence rate in a phase II study, as reported in the 2021 Annals of Oncology guidelines 1. The evidence provided focuses on luspatercept, which has been approved by the FDA and EMA for use in RBC transfusion-dependent, lower-risk MDS patients with ring sideroblasts (MDS-RS) or SF3B1 mutation refractory to erythropoiesis-stimulating agents (ESAs) 1. Key highlights of luspatercept's efficacy include:

• Erythroid response rate of 63% in a phase II study
• RBC transfusion independence rate of 38% in the same study
• Better results in patients with MDS-RS or SF3B1 mutation
• Limited toxicity reported in the phase II study
• Confirmation of results in a phase III placebo-controlled randomized study 1. It is essential to note that while sotatercept is not mentioned in the provided evidence, luspatercept's mechanism of action and clinical benefits may provide insight into the potential effects of similar drugs, such as sotatercept, in treating related conditions.

From the FDA Drug Label

HIGHLIGHTS OF PRESCRIBING INFORMATION These highlights do not include all the information needed to use WINREVAIR safely and effectively. See full prescribing information for WINREVAIR. WINREVAIR™ (sotatercept-csrk) for injection, for subcutaneous use Initial U. S. Approval: 2024 INDICATIONS AND USAGE WINREVAIR is an activin signaling inhibitor indicated for the treatment of adults with pulmonary arterial hypertension (PAH, WHO Group 1) to increase exercise capacity, improve WHO functional class (FC) and reduce the risk of clinical worsening events.

The main highlights for the trial with sotatercept are:

• Indication: Sotatercept is indicated for the treatment of adults with pulmonary arterial hypertension (PAH, WHO Group 1) to increase exercise capacity, improve WHO functional class (FC) and reduce the risk of clinical worsening events.
• Dosage: The recommended starting dose is 0.3 mg/kg by subcutaneous injection, with a recommended target dose of 0.7 mg/kg every 3 weeks.
• Key warnings and precautions include erythrocytosis, severe thrombocytopenia, serious bleeding, embryo-fetal toxicity, and impaired fertility.
• Common adverse reactions include headache, epistaxis, rash, telangiectasia, diarrhea, dizziness, and erythema. 2 2

From the Research

Trial Highlights for Sotatercept

• Sotatercept is an ActRIIA-IgG1 fusion protein trap that has been studied for its effects on hemoglobin concentration, bone mineral density (BMD), and abdominal aortic vascular calcification in patients with end-stage kidney disease (ESKD) 3.
• The REN-001 and REN-002 phase II studies examined the safety, tolerability, and effects of sotatercept in patients with ESKD, with results showing a dose-related increase in hemoglobin concentration and a slowing of vascular calcification 3.
• The most common adverse events during treatment with sotatercept were hypertension, muscle spasm, headache, arteriovenous fistula site complication, and influenza, which were observed in both treatment and placebo groups 3.

Anemia Management in Chronic Kidney Disease

• Anemia is a prevalent and premature comorbidity in chronic kidney disease (CKD) and is associated with multiple adverse clinical consequences, including increased mortality 4.
• Erythropoiesis-stimulating agents (ESAs) and iron supplementation are the cornerstones of therapy for correcting anemia in CKD patients, but there are no generally accepted dosing algorithms for these agents 4.
• Higher hemoglobin targets have been associated with more harm than benefit, including increased risk for stroke, hypertension, and vascular access thrombosis and mortality 5.

Future Directions for Anemia Treatment

• New strategies for managing anemia in CKD are being developed, including hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs), which have shown promise in increasing endogenous erythropoietin production and improving iron availability 6.
• Recent clinical trials have elucidated important aspects of iron supplementation, which may change treatment targets in the future 6.
• Sotatercept, as a first-in-class activin signaling inhibitor, has been studied in a phase III trial for the treatment of pulmonary arterial hypertension (PAH), with results showing no clinically meaningful differences in pharmacokinetics, efficacy, and safety between participants who developed antidrug antibodies and those who did not 7.