A Regulatory Review Approach for Evaluation of Micafungin for Treatment of Neonatal Candidiasis

Pathogenesis of neonatal candidiasis (NC) is distinct from systemic candidiasis in adults and older pediatric patients due to the significant incidence of central nervous system involvement in neonates. Thus, although adequate and well-controlled trials in NC are often unfeasible due to difficulty enrolling patients, extrapolation of efficacy from antifungal drug trials in adults is generally not appropriate. However, treatment of NC is an area of great unmet need. We describe a regulatory review approach that combined the assessment of limited clinical efficacy, pharmacokinetics, and safety data from neonates and young infants along with microbiology outcomes and pharmacokinetic data from relevant nonclinical models of candidemia/invasive candidiasis to inform the use of micafungin in pediatric patients younger than 4 months, while communicating areas of remaining uncertainty in labeling.

Automated summary

The pathogenesis of neonatal candidiasis differs from systemic candidiasis in adults, with a higher incidence of central nervous system involvement. While clinical trials for neonatal candidiasis are challenging, it is important to address the unmet need for effective treatment in this population. A regulatory review approach has been described to guide the use of micafungin in pediatric patients younger than 4 months, while acknowledging areas of uncertainty in labeling.