.png){kind=icon}
.png){kind=icon}
Return
Evolving landscape of drug development for pediatric rare diseases–from successes to strategies for addressing unmet needs
.png){kind=icon}
PRE
AI
S
Y
M
X
S
J
M
C
S
M
G
L
R
J
DOI：10.1016/j.xphs.2026.104401.png)
.png){kind=icon}
Original request for help.png){kind=icon}
Share.png){kind=icon}
Save
Abstract
En 中文
Over 7,000 rare diseases have been identified and 50-75% of them impact pediatrics. Pediatric rare diseases represent a critical unmet need, as nearly 95% of these conditions lack FDA-approved therapies. Progress, through scientific innovation and focused public health initiatives, has contributed to addressing the unmet needs of patients with rare diseases and promoting the development of novel therapies. However, key challenges remain, including demonstrating meaningful effects in small, heterogeneous populations, lack of validated biomarkers, designing trials that maximize patient participation, and optimizing doses often without independent dose-finding studies. In this review, we describe the landscape of FDA-approved products for rare diseases and highlight examples of pediatric drug development where approvals were informed by novel strategies. Acknowledging that rare disease drug development requires flexibility and innovations, these approaches include leveraging adult data for diseases affecting both adults and pediatric populations, extrapolating efficacy and/or safety evidence across pediatric age groups in diseases that occur only in pediatric populations, and the use of mechanistic modeling, biomarkers, innovative trial designs, and new approach methodologies to bridge gaps in knowledge for successful development of drug products for these diseases. Reviews of the ontogeny of drug metabolizing enzymes and transporters that affect drug disposition are summarized to lay the foundation for mechanistic modeling. Lastly, future perspectives illuminate the path forward to meet the unmet medical needs for treating rare pediatric diseases.
Journal
IF:
3.8
Papers:
1.1W
Citations:
2.6W
Organization
Cited Papers