Profile
General Information
Winrevair (sotatercept-csrk) is an activin signaling inhibitor.
Winrevair is specifically indicated for the treatment of adults with pulmonary arterial hypertension (PAH, World Health Organization [WHO] Group 1) to increase exercise capacity, improve WHO functional class (FC), and reduce the risk of clinical worsening events.
Dosing/Administration
- Winrevair is supplied as an injection for subcutaneous administration.
- Winrevair is administered once every 3 weeks by subcutaneous injection according to patient body weight. See drug label for weight-based calculations.
- The recommended starting dose is 0.3 mg/kg by subcutaneous injection. The recommended target dose is 0.7 mg/kg every 3 weeks by subcutaneous injection.
- Dosage modifications due to increased hemoglobin (Hgb) and decreased platelets may be necessary. Check Hgb and platelets before each dose for the first 5 doses, or longer if values are unstable, and monitor periodically thereafter.
Mechanism of Action
Winrevair (sotatercept-csrk), a recombinant activin receptor type IIA-Fc (ActRIIA-Fc) fusion protein, is an activin signaling inhibitor that binds to activin A and other TGF- β superfamily ligands. As a result, sotatercept-csrk improves the balance between the pro-proliferative (ActRIIA/Smad2/3-mediated) and anti-proliferative (BMPRII/Smad1/5/8-mediated) signaling to modulate vascular proliferation. In rat models of PAH, a sotatercept-csrk analog reduced inflammation and inhibited proliferation of endothelial and smooth muscle cells in diseased vasculature. These cellular changes were associated with thinner vessel walls, partial reversal of right ventricular remodeling, and improved hemodynamics.
Side Effects
Adverse effects associated with the use of Winrevair may include, but are not limited to, the following:
- headache
- epistaxis
- rash
- telangiectasia
- diarrhea
- dizziness
- erythema
Clinical Trial Results
The FDA approval of Winrevair was based on the Phase 3 STELLAR trial, which compared Winrevair (n=163) to placebo (n=160), both in combination with background standard of care therapies in adult patients with PAH (WHO Group 1 FC II or III). Results showed adding Winrevair to background therapy increased six-minute walk distance from baseline by 41 meters at Week 24 and significantly improved multiple important secondary outcome measures, including reducing the risk of death from any cause or PAH clinical worsening events by 84% versus background therapy alone (number of events: 9 vs 42).