Merck’s Winrevair a Novel Approach in the Treatment of Pulmonary Arterial Hypertension
Merck’s (NYSE: MRK) Winrevair (sotatercept) is a first-in-class activin signaling inhibitor for pulmonary arterial hypertension (PAH), representing a novel mechanism in the control of PAH.
Winrevair was approved by the FDA in March 2024 for the treatment of adults with PAH. Winrevair had previously been granted breakthrough therapy and orphan drug designations by the FDA. The approval of Winrevair comes on the heels of another novel FDA drug approval for PAH, also in March 2024 — Johnson & Johnson’s (NYSE: JNJ) Opsynvi, a single-tablet combination of macitentan and tadalafil. Merck has set the price of Winrevair at $14,000 per vial. Based on data from clinical trials, Merck expects that most patients will need a single vial every three weeks. Visible Alpha consensus estimates project that Winrevair will generate $397 million in revenue in 2024 and reach peak sales of $7.2 billion in 2035.
Merck integrated Winrevair into its portfolio after acquiring Acceleron Pharma for $11 billion in 2021. Winrevair is under a licensing agreement with Bristol-Myers Squibb (NYSE: BMY), granting BMY exclusive rights for its development and commercialization outside of the pulmonary hypertension field.
About PAH and Activin
PAH stems from narrowed arteries in the lungs, causing shortness of breath, fatigue, a significant strain on the heart, chest pain, exercise limitation, altered quality of life, and markedly reduced life expectancy. The underlying molecular mechanisms that trigger the pathology of PAH is poorly understood. However, the mechanism behind PAH is known to be multifactorial — related to inflammation, impaired angiogenesis, metabolic alterations, and genetic/epigenetic abnormalities, among other factors. Notably, PAH affects women disproportionately — four times more women are affected than men. Based on Merck’s estimates, there are around 40,000 patients with PAH in the U.S. There is no cure for PAH, though available therapies control symptoms and improve quality of life.
Winrevair is a recombinant activin receptor type IIA fusion protein that is an activin signaling inhibitor by binding and sequestering activin A and TGF- β superfamily ligands (it is well established that the TGF- β family plays a significant role in PAH). This Winrevair interaction improves the balance between pro-proliferative and anti-proliferative signaling to modulate vascular proliferation. In rat models of PAH, a Winrevair analog reduced inflammation and inhibited the proliferation of endothelial and smooth muscle cells in diseased vasculature, reducing the pathology of PAH.
