The Role of Biomarkers and Surrogate End Points in Drug Development for Neonatal Pulmonary Arterial Hypertension

Abstract

Pulmonary arterial hypertension (PAH) is a rare disease in newborns, infants, and children. It is associated with significant morbidity and mortality, but has limited treatment options. Except for inhaled nitric oxide, which is approved for persistent pulmonary hypertension of the newborn (PPHN), no drug is approved for the treatment of newborns, infants, and children with PAH. The lack of developmentally appropriate pediatric efficacy end points and pediatric clinical trials contribute to this unmet medical need. The noninvasive biomarkers reported in the literature that can be used as potential surrogate end points to assess disease severity and treatment response in neonates, infants, and children with PAH are reviewed herein. In addition, the role of the US Food and Drug Administration in developing potential biomarkers as surrogate end points to facilitate drug development for the treatment of children with PPHN and PAH in children is reviewed herein.