Winrevair Approved for Pulmonary Arterial Hypertension

On March 26, 2024, the U.S. Food and Drug Administration (FDA) approved Merck’s Winrevair^™ (sotatercept-csrk), an activin signaling inhibitor for treating adults with pulmonary arterial hypertension (PAH). The recommended starting dose is 0.3 mg/kg by subcutaneous (SC) injection every three weeks, which can be further increased to the target dose of 0.7 mg/kg every 3 weeks, labs permitting. The patient’s hemoglobin (Hgb) and platelet levels should be evaluated before receiving at least the first 5 doses, and then periodically thereafter to determine if dose adjustments are needed. Merck plans to make Winrevair available by the end of April 2024 for $14,000 per vial. Full prescribing information can be found here.

At a Glance

• Brand Drug: Winrevair (sotatercept-csrk)
• Manufacturer: Merck
• Date Approved: March 26, 2024
• Indication:  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 Forms Available: Single-dose vials with 45mg and 60mg of Winrevair lyophilized cake or powder for reconstitution.
• Launch Date: By the end of April 2024
• Estimated Annual Cost: The price is estimated to be $14,000 per vial. The annual cost will be approximately $242,000 for a patient weighing 80kg (about 175 pounds).                 
• PAH is one of five kinds of high blood pressure that affects the lungs. Designated as Group I, it causes gradually worsening constriction and thickening of small arteries in the lungs, which eventually weakens the heart.
• With fewer than 1,000 new cases diagnosed annually, many patients are young and middle-aged women, especially those of African and Hispanic heritage. Up to 40,000 Americans are living with PAH. The disease has a 43% five-year mortality rate.
• Winrevair is a fusion protein based on the activin receptor type IIA (ActRIIA), which is the natural high-affinity receptor for activin and other proteins in the Transforming Growth Factor-beta (TGF-beta) superfamily. Combining parts of human ActRIIA and immunoglobulin G1 (IgG1) blocks the activity of activins and growth differentiation factors that contribute to PAH.
• In the STELLAR trial, Winrevair treatment, along with a background standard of care, resulted in an average increase of 41 meters in the 6-minute Walk Distance at Week 24. In addition, treatment leads to about an 85% reduction in the risk of death or PAH clinical worsening, compared to background therapy alone, with an average follow-up of about 32 weeks.
• Winrevair treatment can increase hemoglobin levels, leading to an excess concentration of red blood cells (erythrocytosis). If this becomes severe, it can increase the risk of blood clots or lead to excessive thickening of the blood, known as hyperviscosity syndrome.
• Therapy can also reduce platelet counts, causing severe thrombocytopenia or a low platelet count, which could increase bleeding risk. Treatment with Winrevair should not be started if the patient’s platelet count is below 50,000/mm³.
• Women who may become pregnant should use effective methods of contraception during therapy and for a minimum of four months after treatment stops.
• Winrevair was designated as a Breakthrough Therapy and given Priority Review.