Winrevair (sotatercept)

A first-in-class treatment for adults with PAH (WHO Group 1) that works through an entirely new mechanism. Instead of just dilating blood vessels like older PAH drugs, sotatercept targets the underlying disease biology by rebalancing growth signals in pulmonary artery walls.

In PAH, an imbalance between activin (which promotes abnormal cell growth in artery walls) and BMP signaling (which keeps growth in check) causes the pulmonary arteries to thicken and narrow. Sotatercept acts as a trap for activins, soaking them up before they can drive further vascular remodeling. This restores the balance and can reverse some of the artery wall thickening that drives PAH.

Common side effects include headache, nosebleeds, rash, telangiectasias (small dilated blood vessels on the skin), diarrhea, dizziness, and skin redness. Sotatercept can raise hemoglobin (blood thickening) and lower platelets, so both are checked before each of the first 5 doses and periodically after. Serious bleeding, including stomach and brain bleeding, has occurred, more often in people also taking prostacyclins or blood thinners or with low platelets. It may harm an unborn baby, so effective birth control is needed. The label also warns that it may lower fertility in women and men.

Given as a subcutaneous injection every 3 weeks. Starting dose is 0.3 mg/kg, titrated up to 0.7 mg/kg. Can be self-administered at home after training.

Yes, Sotatercept (Winrevair) is FDA approved (2024) for the treatment of Pulmonary Arterial Hypertension.

Previous PAH drugs (prostacyclins, ERAs, PDE5 inhibitors, sGC stimulators) all work by dilating blood vessels, which relieves symptoms but does not address the underlying disease process. Sotatercept is the first therapy that targets the abnormal cell proliferation driving pulmonary artery wall thickening. By trapping activins and rebalancing growth signals, it can actually reverse some of the vascular remodeling. The STELLAR trial showed the largest improvement in exercise capacity ever seen in a PAH drug trial.

The STELLAR Phase 3 trial demonstrated a 40.8-meter improvement in 6-minute walk distance compared to placebo. It also showed an 84% lower risk of death or PAH clinical worsening and significant improvements in secondary endpoints including pulmonary vascular resistance, NT-proBNP levels, and WHO functional class. A later trial, ZENITH, in high-risk patients found a 76% lower risk of death, lung transplant, or hospitalization for PAH, which the FDA added to the label in October 2025.

Sotatercept is given as a subcutaneous (under the skin) injection every 3 weeks. The dose is based on body weight, starting at 0.3 mg/kg and titrated up to 0.7 mg/kg. After training, patients can self-administer at home. This is more convenient than IV prostacyclins but requires regular injections compared to daily oral pills.

No. Sotatercept was studied on top of existing PAH medications, not as a replacement. In the STELLAR trial, patients were on stable background therapy (typically combinations of ERAs, PDE5 inhibitors, and/or prostacyclins) when sotatercept was added. The benefit was additive to what background therapy was already providing. Patients should continue their existing PAH medications unless directed otherwise by their physician.

The most notable side effects are increased hemoglobin (blood thickening), which may require dose adjustment, and decreased platelet counts. Nosebleeds (epistaxis) are common. Telangiectasias (small visible blood vessels on the skin) have been reported. Hemoglobin levels should be monitored regularly, and the dose should be adjusted if hemoglobin rises above target ranges. Dizziness and headache can also occur.