Sotatercept Gains European Approval for PAH for Use With Other Treatments

Europe’s drug approval agency has granted approval to sotatercept (Winrevair; Merck) as a combination treatment for certain use in pulmonary arterial hypertension (PAH).¹

With the agency’s green light, sotatercept is the first activin signaling inhibitor therapy approved for the disease in Europe, now approved for patients with World Health Organization Functional Class (FC) II to III disease. The approval comes months after the FDA’s approval of the treatment. The approvals of sotatercept are based on findings from the phase 3 STELLAR trial.^2,3

Months after the FDA's approval of sotatercept for treating PAH, the drug has gained European approval | image credit: wladimir1804 - stock.adobe.com

“Pulmonary arterial hypertension is a devastating disease for patients, who suffer from debilitating symptoms that severely limit their daily activities,” said Dr. Marc Humbert, Professor of Medicine and Director of Pulmonary Hypertension Reference Center at Université Paris-Saclay, in a statement. “New treatment options continue to be needed for patients. Based on the Phase 3 STELLAR study, adding WINREVAIR to background PAH therapy improved exercise capacity, reduced the risk of death or clinical worsening events and improved functional class compared to background PAH therapy alone. There findings are significant and reinforce that WINREVAIR, in combination with other PAH therapies, should be considered as a new standard of care for the treatment of functional class II and III adult patients.”

Treatments for PAH include phosphodiesterase-5 inhibitors, endothelin-receptor antagonists, soluble guanylate cyclase stimulators, and compounds targeting the prostacyclin pathway. However, while these treatments—used alone or in combination—have historically improved exercise capability and progression-free survival, improvements in survival have lagged over the last decade, leaving room for newer treatments that address the disease differently.

Sotatercept is a first-of-its-kind treatment that inhibits certain proteins largely responsible for the development of PAH. It is given as a subcutaneous injection once every 3 weeks and can be administered by the patient or caregiver.

Data from the randomized, multicenter, double-blind STELLAR trial showed that sotatercept improved 6-minute walk distance, the study’s primary endpoint, across prespecified subgroups of patients, even among those receiving triple background therapy, the maximum amount of treatment given to patients with the disease.

The trial included 323 patients, randomized 1:1 to receive sotatercept or placebo. Overall, the mean change in 6-minute walk distance between baseline and 24 weeks was 40.1 meters, correlating to approximately 132 feet (95% CI, 29.9-50.2), for patients receiving sotatercept. Meanwhile, distance dropped 1.4 meters, correlating to approximately 5 feet, during the same period for patients receiving placebo.

The drug reduced the risk of death or nonfatal clinical worsening by 84% compared with placebo (HR, 0.16; 95% CI, 0.08-0.35).

The most common adverse reactions associated with sotatercept in the trial, occurring in ≥10% of patients and at least 5% more than placebo, were headache (24.5% vs 17.5%), epistaxis (22.1% vs 1.9%), rash (20.2% vs 8.1%), telangiectasia (16.6% vs 4.4%), diarrhea (15.3% vs 10%), dizziness (14.7% vs 6.2%), and erythema (13.5% vs 3.1%).

“The adverse-event profile that was observed with sotatercept treatment was generally consistent with that reported in previous studies of sotatercept,” noted the researchers of the STELLAR trial.“Increases in hemoglobin levels, a known effect of sotatercept, were reported as adverse events in 5.5% and 6.1% of the patients who received the trial drug through week 24 and trial completion, respectively. These increases were manageable with dose interruptions or reductions and were not associated with treatment discontinuations.”

References:

1. Merck. Merck receives European Commission Approval for WINREVAIR™ (sotatercept) in combination with other pulmonary arterial hypertension (PAH) therapies, for the treatment of PAH in adult patients with Functional Class II-III. August 26, 2024. Accessed August 30, 2024. https://www.merck.com/news/merck-receives-european-commission-approval-for-winrevair-sotatercept-in-combination-with-other-pulmonary-arterial-hypertension-pah-therapies-for-the-treatment-of-pah-in-adult-patients-w/
2. Merck. FDA approves Merck’s WINREVAIR™ (sotatercept-csrk), a first-in-class treatment for adults with pulmonary arterial hypertension (PAH, WHO* Group 1). March 26, 2024. Accessed August 30, 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/
3. Hoeper MM, Badesch DB, Ghofrani HA, et al. Phase 3 trial of sotatercept for treatment of pulmonary arterial hypertension. N Engl J Med. 2023;388(16):1478-1490. doi:10.1056/NEJMoa2213558