New therapy shows dramatic survival benefits in advanced pulmonary arterial hypertension

A relatively new therapy used to treat pulmonary arterial hypertension in those with mild to moderate disease was found to be effective at preventing death in those with more advanced disease. Results were published on Wednesday, May 28, in The New England Journal of Medicine and could have "transformative implications" for patients, according to an editorial that accompanied the study written by Bradley Maron, MD, Professor of Medicine and Director of the Hypertension Program at the University of Maryland School of Medicine.

When the US Food and Drug approved the first-in-its-class drug, called sotatercept, last year, it was indicated only for those with mild pulmonary arterial hypertension to increase exercise capacity and prevent clinical worsening of the lung condition which is rare but progressive, often leading to premature death. About 1,000 Americans are diagnosed with the condition every year, and women under age 60 are at higher risk. The condition, caused by a narrowing of small arteries throughout the lungs, triggers the heart to work harder and eventually lose its ability to effectively pump blood.

The clinical trial, called Zenith, was led by researchers in France and conducted at several clinical sites in the U.S. and internationally. It involved 172 patients with advanced pulmonary arterial hypertension who were randomly assigned to get an injection of sotatercept along with their usual treatments or to get a placebo injection along with their usual treatments.

"The authors observed a 76 percent lower risk of a primary endpoint event [death from any cause, lung transplantation, or hospitalization] with sotatercept than with a placebo – a staggering effect by any standard by uniquely relevant in pulmonary arterial hypertension, since previous trials have typically shown comparatively modest results with weaker end points," wrote Dr. Maron, who is also Director of the University of Maryland Institute for Health Computing. Dr. Maron was not involved in the study and provided an independent assessment of the study findings.

The trial was stopped early after it became clear that the sotatercept group had significant benefits over those taking a placebo: 50 percent of the placebo group were hospitalized during the trial compared to only 9 percent of the sotatercept group. Death occurred in 15 percent of those on a placebo compared to 8 percent of those on sotatercept.

Vascular malformations and bleeding events occurred in some patients taking sotatercept, but this did not lead them to stop taking the drug. Nonetheless, better understanding of how these side effects could relate to patient adherence to sotatercept in actual clinical practice is needed, according to Dr. Maron.

"Results from the Zenith trial," he wrote, "offer a key measure of optimism to patients with advanced-stage pulmonary arterial hypertension with limited or no options."