Article Impact Level: HIGH Data Quality: STRONG Summary of New England Journal of Medicine, 0(0). https://doi.org/10.1056/NEJMoa2415160 Dr. Marc Humbert et al.
Points
- This phase 3 trial evaluated the efficacy of add-on sotatercept in patients with advanced pulmonary arterial hypertension (PAH) at high risk of death, with 172 patients randomized to receive sotatercept or placebo.
- The primary outcomes showed a significant reduction in death, lung transplantation, or hospitalization for worsening PAH in the sotatercept group, with 17.4% of patients experiencing an event compared to 54.7% in the placebo group.
- The sotatercept group had lower rates of death (8.1% vs. 15.1%), lung transplantation (1.2% vs. 7.0%), and hospitalization for worsening PAH (9.3% vs. 50.0%) compared to the placebo group.
- These findings suggest that sotatercept significantly reduced the risk of adverse outcomes in high-risk PAH patients on maximal background therapy, with the most common side effects being epistaxis and telangiectasia.
- The trial was stopped early after an interim analysis showed the potent efficacy of sotatercept, highlighting its potential as an effective add-on therapy for patients with advanced PAH.
Summary
This phase 3 trial aimed to evaluate the efficacy of add-on sotatercept in patients with advanced pulmonary arterial hypertension (PAH) and a high risk of death. Eligible participants had World Health Organization (WHO) functional class III or IV PAH and a high 1-year risk of death, as determined by the Registry to Evaluate Early and Long-Term Pulmonary Arterial Hypertension Disease Management Lite 2 risk score (≥9). A total of 172 patients were randomized to receive sotatercept or placebo, with primary outcomes including a composite of death from any cause, lung transplantation, or hospitalization for worsening PAH. The primary endpoint was assessed in a time-to-first-event analysis.
The results showed a significant reduction in the primary endpoint for the sotatercept group compared to the placebo group. Specifically, 17.4% of patients in the sotatercept group experienced at least one primary endpoint event, compared to 54.7% in the placebo group (hazard ratio, 0.24; 95% CI, 0.13 to 0.43; P<0.001). Death from any cause occurred in 8.1% of sotatercept-treated patients versus 15.1% in the placebo group. Lung transplantation was required in 1.2% of the sotatercept group and 7.0% of the placebo group. In comparison, 9.3% of patients in the sotatercept group were hospitalized for worsening PAH, compared to 50.0% in the placebo group.
These results suggest that sotatercept significantly reduced the risk of death, lung transplantation, and hospitalization for worsening PAH in high-risk patients already on maximal background therapy. The most common adverse events associated with sotatercept were epistaxis and telangiectasia. The trial was stopped early after an interim analysis indicated strong efficacy of sotatercept. These findings highlight the potential of sotatercept as an add-on therapy for patients with advanced PAH.
Link to the article: https://www.nejm.org/doi/full/10.1056/NEJMoa2415160
References Humbert, M., McLaughlin, V. V., Badesch, D. B., Ghofrani, H. A., Gibbs, J. S. R., Gomberg-Maitland, M., … Hoeper, M. M. (n.d.). Sotatercept in Patients with Pulmonary Arterial Hypertension at High Risk for Death. New England Journal of Medicine, 0(0). https://doi.org/10.1056/NEJMoa2415160
