Sotatercept, sold under the brand name Winrevair, is a

medication Medication (also called medicament, medicine, pharmaceutical drug, medicinal product, medicinal drug or simply drug) is a drug used to medical diagnosis, diagnose, cure, treat, or preventive medicine, prevent disease. Drug therapy (pharmaco ...

used for the treatment of

pulmonary arterial hypertension Pulmonary arterial hypertension (PAH) is a syndrome in which the blood pressure in the pulmonary arteries and pulmonary arterioles (the blood vessels located proximal to the capillary bed, the site of oxygen exchange in the lungs) is elevated. T ...

. It is an

activin Activin and inhibin are two closely related protein complexes that have almost directly opposite biological effects. Identified in 1986, activin enhances FSH biosynthesis and secretion, and participates in the regulation of the menstrual c ...

signaling inhibitor, based on the extracellular domain of the

activin type 2 receptor The activin type 2 receptors belong to a larger TGF-beta receptor family and modulate signals for transforming growth factor beta ligands. These receptors are involved in a host of physiology, physiological processes including, cell growth, growt ...

expressed as a recombinant fusion protein with immunoglobulin Fc domain (ACTRIIA-Fc). It is given by

subcutaneous injection Subcutaneous administration is the insertion of medications beneath the skin either by injection or infusion. A subcutaneous injection is administered as a bolus (medicine), bolus into the subcutis, the layer of skin directly below the dermis and ...

. The most common side effects include

headache A headache, also known as cephalalgia, is the symptom of pain in the face, head, or neck. It can occur as a migraine, tension-type headache, or cluster headache. There is an increased risk of Depression (mood), depression in those with severe ...

epistaxis A nosebleed, also known as epistaxis, is an instance of bleeding from the nose. Blood can flow down into the stomach, and cause nausea and vomiting. In more severe cases, blood may come out of both nostrils. Rarely, bleeding may be so significan ...

(nosebleed),

rash A rash is a change of the skin that affects its color, appearance, or texture. A rash may be localized in one part of the body, or affect all the skin. Rashes may cause the skin to change color, itch, become warm, bumpy, chapped, dry, cracke ...

telangiectasia Telangiectasias (), also known as spider veins, are small dilated blood vessels that can occur near the surface of the skin or mucous membranes, measuring between 0.5 and 1 millimeter in diameter. These dilated blood vessels can develop anywhere ...

(spider veins),

diarrhea Diarrhea (American English), also spelled diarrhoea or diarrhœa (British English), is the condition of having at least three loose, liquid, or watery bowel movements in a day. It often lasts for a few days and can result in dehydration d ...

dizziness Dizziness is an imprecise term that can refer to a sense of disorientation in space, vertigo, or lightheadedness. It can also refer to Balance disorder, disequilibrium or a non-specific feeling, such as giddiness or foolishness. Dizziness is a ...

, and

erythema Erythema (, ) is redness of the skin or mucous membranes, caused by hyperemia (increased blood flow) in superficial capillaries. It occurs with any skin injury, infection, or inflammation. Examples of erythema not associated with pathology inc ...

(redness of the skin). Sotatercept was approved for medical use in the United States in March 2024, and in the European Union in August 2024. The US

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respo ...

(FDA) considers it to be a

first-in-class medication A first-in-class medication is a prototype drug that uses a "new and unique mechanism of action" to treat a particular medical condition. While the Food and Drug Administration's Center for Drug Evaluation and Research tracks first-in-class medic ...

Medical uses

In the United States, sotatercept is

indicated In medicine, an indication is a valid reason to use a certain test, medication, procedure, or surgery. There can be multiple indications to use a procedure or medication. An indication can commonly be confused with the term diagnosis. A diagnosis ...

for the treatment of adults with pulmonary arterial hypertension (PAH, WHO Group 1). In the European Union, sotatercept, in combination with other pulmonary arterial hypertension therapies, is indicated for the treatment of pulmonary arterial hypertension in adults with WHO Functional Class (FC) II to III, to improve exercise capacity.

Side effects

The most common adverse reactions include headache, epistaxis, rash, telangiectasia, diarrhea, dizziness, and erythema. Sotatercept causes increases in hemoglobin (red blood cells). High concentrations of red blood cells in blood may increase the risk of blood clots. Sotatercept causes decreases in platelet count, which can result in bleeding problems. Based on findings in animal studies, sotatercept may impair female and male fertility and cause fetal harm when administered during pregnancy.

History

The US

(FDA) approved sotatercept based on evidence of safety and effectiveness from a clinical trial of 323 participants with PAH (WHO group 1 functional class II or III). The trial was conducted at 126 sites in 21 countriesArgentina, Australia, Belgium, Brazil, Canada, the Czech Republic, France, Germany, Israel, Italy, Mexico, the Netherlands, New Zealand, Poland, Serbia, South Korea, Spain, Sweden, Switzerland, the United Kingdom, and the United States. The study included 88 participants inside the United States (43 in the sotatercept group and 45 in the placebo group).

Society and culture

Legal status

Sotatercept was approved for medical use in the United States in March 2024. The FDA granted the application

breakthrough therapy Breakthrough therapy is a United States Food and Drug Administration designation that expedites drug development that was created by Congress under Section 902 of the 9 July 2012 Food and Drug Administration Safety and Innovation Act. The FDA's "b ...

designation. In June 2024, the

Committee for Medicinal Products for Human Use The Committee for Medicinal Products for Human Use (CHMP), formerly known as the Committee for Proprietary Medicinal Products (CPMP), is the European Medicines Agency's committee responsible for elaborating the agency's opinions on all issues regar ...

of the

European Medicines Agency The European Medicines Agency (EMA) is an agency of the European Union (EU) in charge of the evaluation and supervision of pharmaceutical products. Prior to 2004, it was known as the European Agency for the Evaluation of Medicinal Products ...

adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Winrevair, intended for the treatment of pulmonary arterial hypertension. The applicant for this medicinal product is Merck Sharp & Dohme B.V. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged. Sotatercept was authorized for medical use in the European Union in August 2024.

Economics

Following its approval in 2024, the list price of Winrevair as single-vial and double-vial kit was announced at per vial, with an estimated annual cost of $240,000 a year.

Names

Sotatercept is the international nonproprietary name. Sotatercept is sold under the brand name Winrevair.

Research

It was initially developed to increase

bone density Bone density, or bone mineral density, is the amount of bone mineral in bone tissue. The concept is of mass of mineral per volume of bone (relating to density in the physics sense), although medicine#Clinical practice, clinically it is measured by ...

but during its early development was found to increase hemoglobin and red blood cell counts, and was subsequently studied for use in

anemia Anemia (also spelt anaemia in British English) is a blood disorder in which the blood has a reduced ability to carry oxygen. This can be due to a lower than normal number of red blood cells, a reduction in the amount of hemoglobin availabl ...

associated with multiple conditions including

beta thalassemia Beta-thalassemia (β-thalassemia) is an genetic disorder, inherited hemoglobinopathy, blood disorder, a form of thalassemia resulting in variable outcomes ranging from clinically asymptomatic to severe anemia individuals. It is caused by reduce ...

and

multiple myeloma Multiple myeloma (MM), also known as plasma cell myeloma and simply myeloma, is a cancer of plasma cells, a type of white blood cell that normally produces antibody, antibodies. Often, no symptoms are noticed initially. As it progresses, bone ...

. Development of this drug was superseded by the development of luspatercept (Reblozyl), a modified activin receptor type 2B (ACTRIIB-Fc) based ligand trap with improved properties for anemia. Hypothesizing that this drug might block the effects of activin in promoting pulmonary vascular disease, this molecule was found to inhibit vascular obliteration in multiple models of experimental pulmonary hypertension, providing rationale to reposition sotatercept for PAH in the PULSAR and STELLAR clinical trials for PAH.

References

External links

{{Authority control Antihypertensive agents Drugs developed by Merck & Co. Peptides Orphan drugs