Sotatercept

WINREVAIR™ is indicated for the treatment of adults with pulmonary arterial hypertension (PAH, Group 1 pulmonary hypertension) to improve exercise capacity and World Health Organization (WHO) functional class (FC), and reduce the risk of clinical worsening events including hospitalization for PAH, lung transplantation and death. WINREVAIR is an activin signaling inhibitor indicated for the treatment of adults with pulmonary arterial hypertension (PAH, WHO Group 1 pulmonary hypertension) to improve exercise capacity and WHO functional class (FC), and reduce the risk of clinical worsening events, including hospitalization for PAH, lung transplantation and death.

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.

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. See full prescribing information for preparation and administration instructions.

WINREVAIR is contraindicated in patients with serious hypersensitivity (i.e., anaphylaxis, angioedema) to sotatercept-csrk or any of its excipients

Hypersensitivity: Serious hypersensitivity reactions (including anaphylaxis and angioedema) have been reported. Erythrocytosis: If severe, may increase the risk of thromboembolic events and hyperviscosity syndrome. Monitor Hgb before each dose for the first 5 doses, or longer if values are unstable, and periodically thereafter to determine if dose adjustments are required. Severe Thrombocytopenia: May increase the risk of bleeding. Monitor platelets before each dose for the first 5 doses, or longer if values are unstable, and periodically thereafter to determine if dose adjustments are required. Serious Bleeding: Serious bleeding events were reported. Do not administer WINREVAIR if the patient is experiencing serious bleeding. Embryo-Fetal Toxicity: May cause fetal harm. Advise females of reproductive potential of the potential risk to a fetus and use of effective contraception.

The following clinically significant adverse reactions are described elsewhere in the labeling: Hypersensitivity Erythrocytosis Severe Thrombocytopenia Serious Bleeding Embryo-Fetal Toxicity Impaired Fertility The most common (≥10% in patients receiving WINREVAIR and 5% more than placebo) adverse reactions were infections, epistaxis, telangiectasia, diarrhea, headache, rash, increased hemoglobin, dizziness, erythema, gastrointestinal tract bleeding, and gingival bleeding.

Store vials refrigerated at 2°C to 8°C (36°F to 46°F) in original carton to protect from light. Do not freeze. The kit should remain in the refrigerator until ready for use. The unused kit can be out of the refrigerator for (up to 25°C/77°F) up to 24 hours. For additional information on temperature excursions, call Merck Sharp & Dohme LLC at 1-800-672-6372.