A new study found that long-term treatment with sotatercept, a biologic that targets activin signaling to help reverse vascular remodeling in pulmonary arterial hypertension, maintained improvements in exercise capacity and cardiac biomarkers in adults, while demonstrating a consistent safety profile over one year.
The findings are based on data from an ongoing international trial involving 426 patients who had previously completed sotatercept studies. Participants received subcutaneous sotatercept every 21 days and were followed for a mean of 448.6 days, totaling 523 patient-years of exposure. This study assessed its long-term safety and sustained efficacy when used alongside standard pulmonary arterial hypertension (PAH) therapies.
After one year, patients continued to show improvements in key measures. In the group that previously received placebo and then crossed over to sotatercept, mean 6-minute walk distance (6MWD) improved from 404.5 meters at baseline to 455.3 meters. Median N-terminal pro-brain natriuretic peptide (NT-proBNP) levels dropped from 1137.5 pg/mL to 102 pg/mL. Patients who had already been receiving sotatercept maintained similar values over time.
The percentage of participants with mild symptoms (World Health Organization Functional Class I/II) increased from 51% at baseline to 79.9% at one year in the placebo-crossed group. The proportion meeting all three criteria for a low-risk status (WHO Functional Class I/II, 6MWD >440 m, NT-proBNP <300 pg/mL) rose from 18.9% to 42.2%.
Regarding safety, 90.8% of participants experienced at least one treatment-emergent adverse event (TEAE), most of which were mild or moderate. The most common TEAEs were epistaxis (22.1%), COVID-19 (19%), telangiectasia (17.4%), and headache (16.0%). Serious TEAEs occurred in 30.3% of participants. A total of 3.5% discontinued treatment due to adverse events, and 12 deaths (2.8%) were reported, none of which were considered related to sotatercept by study investigators.
Serious bleeding events occurred in 5.2% of participants, with gastrointestinal and pulmonary bleeding being most common. Many of these patients were also receiving prostacyclin or anticoagulants. Four bleeding events (0.9%) were considered treatment-related, and two (0.5%) led to treatment discontinuation.
Telangiectasia, a protocol-specified adverse event of interest, occurred in 28.6% of patients, including 16.9% with new events during the study. All cases were non-serious, and only one led to treatment discontinuation. Most cases were managed with protocol-directed dose adjustments.
Clinical worsening occurred in 4.7% of participants, with a median time to event of 35.6 weeks. Among those on prostacyclin at baseline (67.1%), 5.4% had a ≥10% dose reduction, and 4.0% had a ≥10% dose increase during the study.
The study is ongoing and will follow participants for up to seven years. These interim results support the sustained clinical benefit and manageable safety profile of sotatercept as an add-on therapy in patients with PAH.
Full disclosures can be found in the published study.
Source: ERS Publications
