FDA Approves Sotatercept-csrk for Pulmonary Arterial Hypertension


The drug had previously been granted a breakthrough therapy designation by the FDA.

The FDA has approved Merck’s sotatercept-csrk (Winrevair) for the treatment of pulmonary arterial hypertension (PAH) in adults. The treatment is intended to increase exercise capacity, improve WHO functional class, and reduce the risk of clinical worsening events.1

The drug had previously been granted a breakthrough therapy designation by the FDA. It is the first agency approved activin signaling inhibitor therapy for PAH, “representing a new class of therapy that works by improving the balance between pro- and anti-proliferative signaling” to regulate the vascular cell proliferation that underlies PAH.

Pulmonary arterial hypertension is a rare, progressive disease. | Image credit: Orawan - stock.adobe.com

Pulmonary arterial hypertension is a rare, progressive disease. | Image credit: Orawan - stock.adobe.com

According to the American Lung Association, PAH—a rare, progressive disorder—is most common in women between ages 30 and 60 years, and there are between 500 and 1000 new cases of PAH diagnosed each year in the United States. The exact cause of the disease is unknown, but researchers hypothesize that PAH results from injury to the cells lining the blood vessels of the lung, causing blood vessel disease over time.2

“Pulmonary arterial hypertension is a rare, progressive, and ultimately life-threatening disease in which blood vessels in the lungs thicken and narrow, causing significant strain on the heart,” said Marc Humbert, MD, PhD, professor of medicine and director of the Pulmonary Hypertension Reference Center at the Université Paris-Saclay.

READ MORE: Exploring Geographic Barriers to Care Access for Patients With Pulmonary Arterial Hypertension

Humbert was also an investigator on the phase 3 STELLAR clinical trial (NCT04576988), the global, double-blind, placebo-controlled, multicenter, parallel-group clinical trial evaluating the drug. The study enrolled 323 adults and compared sotatercept-csrk (n=163) to placebo (n=160) in combination with background standard of care in adults with PAH (World Health Organization Group 1 Functional Class II or III). The primary efficacy end point in the study was the change from baseline at week 24 in the 6-minute walk distance (6MWD).

In the treatment group, results demonstrated that adding sotatercept-csrk to standard of care therapy increased 6MWD by 41 meters at week 24 (95% CI, 28-54), Patients in the treatment group also experienced an improvement in functional class from baseline to week 24 (29% vs 14% of patients in the placebo group), an 84% reduction in the occurrence of death or PAH clinical worsening events (median duration of exposure, 33.6 weeks; number of events, 9 vs 42 in the treatment and placebo groups, respectively; HR, 0.16; 95% CI, 0.08-0.35). Patients also experienced an improvement from baseline pulmonary vascular resistance, with a median treatment difference of -235 dynes*sec/cm5 (95% CI, -288 to -181) and an improvement from baseline N-terminal pro-B-type natriuretic peptide (median treatment difference, -442 pg/mL; 95% CI, -574 to -310).

“Adding [sotatercept-csrk] to background PAH therapy demonstrated significant clinical benefits compared to background PAH therapy alone,” Humbert added. “This approval is an important milestone, as it offers healthcare providers a novel therapeutic option that targets a new PAH treatment pathway.”

Matt Gratano, president and CEO of the Pulmonary Hypertension Association, also applauded the approval. “A diagnosis of PAH is a life-changing experience for patients and families due to its chronic, progressive nature…. We are excited to see industry research leading to a better understanding of PAH and the development of a medicine in a novel treatment pathway that expands options for the patient community.”

Sotatercept-csrk is administered once every 3 weeks via subcutaneous injection; it may be administered by patients or caregivers with guidance, training, and follow up from a health care provider. Providers should monitor both hemoglobin and platelets before each dose for the first 5 doses—or longer if values are unstable—as well as periodically thereafter to determine if dose adjustments are needed. Sotatercept-csrk may increase hemolgobin and may lead to erythrocytosis; if severe, it may increase the risk of thromboembolic events or hyperviscosity syndrome. Decreased platelet counts may lead to severe thrombocytopenia, which can increase the risk of bleeding.

“New treatment options continue to be needed for patients with [PAH] that support important clinical goals, including increasing exercise capacity and improving functional class,” said Aaron Waxman, MD, PhD, study investigator and executive director of the Center for Pulmonary Heart Diseases at Brigham and Women’s Hospital in Boston, Massachusetts. “Sotatercept added to background therapy has the potential to become a new standard of care option for patients with PAH.”

READ MORE: Cardiology Resource Center

1. FDA approves Merck’s Winrevair (sotatercept-csrk), a first-in-class treatment for adults with pulmonary arterial hypertension (PAH, WHO*Group 1). News release. Merck. March 26, 2024. Accessed March 27, 2024. https://www.merck.com/news/fda-approves-mercks-winrevair-sotatercept-csrk-a-first-in-class-treatment-for-adults-with-pulmonary-arterial-hypertension-pah-who-group-1/
2. Learn more about pulmonary arterial hypertension. American Lung Association. Updated June 8, 2023. Accessed March 27, 2024. https://www.lung.org/lung-health-diseases/lung-disease-lookup/pulmonary-arterial-hypertension/learn-about-pulmonary-arterial-hypertension 
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