Johanna Schulz, Veronika C. Stark, Lars Harbaum, Rainer Kozlik-Feldmann, Thomas S. Mir, Fridrike Stute, Jakob Olfe
University Heart & Vascular Center Hamburg. University Medical Centre Hamburg-Eppendorf Hamburg.
Germany
Children
Children 2026; 13:
DOI: 10.3390/children13040465
Abstract
Background/objectives: Pulmonary arterial hypertension (PAH) is a rare but life-threatening disease that presents particular therapeutic challenges in children. It is characterized by pulmonary vasoconstriction and vascular remodeling, leading to right ventricular strain and eventually right heart failure. Although advances in pharmacotherapy have improved outcomes, treatment options remain limited. This review aims to evaluate the potential role of sotatercept, a novel fusion protein recently approved for adult PAH, and to assess the translatability of adult data to the pediatric population.
Methods: A narrative synthesis of preclinical studies and randomized controlled trials was conducted to summarize the current evidence on sotatercept. In addition, pathophysiological, developmental, and therapeutic differences between adult and pediatric PAH were critically examined to assess relevance and applicability to younger patients.
Results: Clinical trials in adults (PULSAR, STELLAR, ZENITH, HYPERION) confirm sotatercept’s efficacy on background therapy, with significant reductions in pulmonary vascular resistance, improvements in 6 min walk distance, enhanced right ventricular function, and risk reductions in clinical worsening events. However, extrapolation to pediatric PAH faces challenges including etiological differences (e.g., PAH-CHD predominance, PPHN in infants), age-inappropriate endpoints (e.g., 6MWD infeasible in young children), variable growth-related pharmacokinetics, and compensatory RV physiology delaying overt failure. Safety concerns are manageable in adults but raise pediatric-specific alarms: activin inhibition’s theoretical tumorigenic potential (dual tumor suppressor/promoter role), pubertal/fertility disruption (FSH suppression, gonadal maturation delay), and skeletal growth interference-unproven clinically yet demanding long-term monitoring. The ongoing MOONBEAM trial will provide initial pharmacokinetic/safety data in children.
Conclusions: Sotatercept represents a promising, first-in-class therapeutic option for PAH with the potential to transform disease management. Nevertheless, dedicated pediatric studies are crucial to confirm safety, efficacy, and appropriate dosing and to define its role in the long-term treatment of children with PAH.
Category
Medical Therapy. Efficacy or Lack of Efficacy
Medical Therapy. Adverse Effects or Lack of Adverse Effects
Review Articles Concerning Pulmonary Vascular Disease
Age Focus: Pediatric Pulmonary Vascular Disease
Fresh or Filed Publication: Fresh (PHresh). Less than 1-2 years since publication
Article Access
Free PDF File or Full Text Article Available Through PubMed or DOI: Yes