From the Research
Sotatercept is expected to cause elevation of serum proteins, particularly hemoglobin, as this is its intended therapeutic effect, and patients should be monitored regularly for changes in hemoglobin levels and other serum proteins involved in erythropoiesis and iron metabolism. Sotatercept is a novel activin receptor type IIA fusion protein that acts as a ligand trap, inhibiting TGF-beta superfamily signaling and promoting erythropoiesis (red blood cell production) 1. When used for pulmonary arterial hypertension or anemia in certain conditions, sotatercept typically increases hemoglobin levels by 1-2 g/dL within weeks of initiation, as seen in a phase 3 trial where it resulted in a lower risk of a composite of death from any cause, lung transplantation, or hospitalization for worsening pulmonary arterial hypertension than placebo 1. This elevation is expected and monitored as part of treatment. Patients receiving sotatercept should have regular blood work to monitor hemoglobin levels, with dose adjustments if levels rise too quickly or exceed target ranges. The medication is typically administered as a subcutaneous injection at doses ranging from 0.3-0.7 mg/kg every 3 weeks, depending on the condition being treated.
Key Points
- Sotatercept increases hemoglobin levels by promoting erythropoiesis
- Regular monitoring of hemoglobin levels and other serum proteins is necessary
- Dose adjustments may be needed if hemoglobin levels rise too quickly or exceed target ranges
- Sotatercept is administered as a subcutaneous injection at doses ranging from 0.3-0.7 mg/kg every 3 weeks
Mechanism of Action
Sotatercept's mechanism of action involves inhibiting TGF-beta superfamily signaling, which reduces inhibitory signals in bone marrow precursor cells and promotes effective erythropoiesis 2. This leads to an increase in hemoglobin levels and other serum proteins involved in erythropoiesis and iron metabolism.
Clinical Implications
The use of sotatercept has been shown to improve exercise capacity and delay the time to clinical worsening in patients with pulmonary arterial hypertension 1. It has also been approved for the treatment of adults with pulmonary arterial hypertension (PAH) Group 1, on top of background PAH therapy to increase exercise capacity, improve WHO functional class and reduce the risk of clinical worsening events 2.