TOPLINE: 

Compared with placebo, sotatercept added to standard therapy within the first year after diagnosis of pulmonary arterial hypertension reduced the risk for clinical worsening events in patients with an intermediate or high risk for death.

METHODOLOGY:

• Researchers conducted a phase 3 randomized trial to assess the efficacy and safety of sotatercept in patients with World Health Organization functional class II or III group 1 pulmonary arterial hypertension.
• Overall, 320 patients whose disease had been diagnosed within the past year and who had an intermediate or high risk for death and were receiving double or triple background therapy for at least 90 days were randomly assigned to receive subcutaneous sotatercept or placebo as an add-on therapy every 21 days.
• The median follow-up duration was 14.6 months in the sotatercept group and 11.5 months in the placebo group.
• The primary endpoint was clinical worsening, a composite of death, unplanned hospitalization for at least 24 hours for worsening pulmonary arterial hypertension, atrial septostomy, lung transplantation, or deterioration in exercise testing performance.

TAKEAWAY:

• Clinical worsening events occurred in 10.6% of patients in the sotatercept group vs 36.9% of those in the placebo group (hazard ratio, 0.24; P < .001). Deterioration in exercise testing performance and unplanned hospitalizations occurred in fewer patients in the sotatercept group than the placebo group.
• More patients in the sotatercept group than the placebo group had multicomponent improvement and a low Registry to Evaluate Early and Long-Term Pulmonary Arterial Hypertension Disease Management Lite 2 risk score at week 24.
• Treatment discontinuation due to adverse events occurred in 3.1% of patients in the sotatercept group vs none in the placebo group.
• Adverse events deemed to be related to sotatercept or placebo were more frequent in the sotatercept group (57.5% vs 30.0%), and adverse events leading to death occurred in 2.5% of patients in the sotatercept group vs 3.1% in the placebo group.

IN PRACTICE:

“Among adults with pulmonary arterial hypertension who had received the diagnosis less than 1 year earlier, the addition of sotatercept to background therapy resulted in a lower risk of clinical worsening than placebo,” the authors wrote.

SOURCE:

The study was led by Vallerie V. McLaughlin, MD, University of Michigan Medical School, Ann Arbor, Michigan. It was published online on September 30, 2025, in The New England Journal of Medicine.

LIMITATIONS: 

Early termination of the trial reduced the follow-up duration and limited enrollment, affecting assessments of longer-term safety and efficacy. Additionally, 33 patients did not reach the week-24 visit due to early trial termination. Secondary endpoints were tested at 24 weeks, precluding assessment of longer-term efficacy. 

DISCLOSURES:

The study was funded by Merck Sharp & Dohme, a subsidiary of Merck in Rahway, New Jersey. Several authors reported being Merck employees or holding Merck stock or stock options. Some other authors disclosed relationships with various pharmaceutical companies including employment; ownership of stock or stock options; consulting, advisory, or steering committee roles; and receipt of lecture fees and institutional research grants. 

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.