Emerging FGFR3-Targeted Therapies

In “Emerging FGFR3-Targeted Therapies,” our panel explores investigational approaches designed to inhibit the abnormal FGFR3 signaling that drives achondroplasia. The discussion begins with infigratinib, an orally bioavailable tyrosine kinase inhibitor being evaluated in children with achondroplasia. The panel describes its development through natural history and dose-finding studies before progression into phase 3 evaluation. Unlike CNP-pathway therapies, which counteract downstream effects of excessive FGFR3 signaling, infigratinib is designed to act more directly on the receptor pathway itself. The experts discuss annualized height velocity as a key clinical trial endpoint and consider what the emerging results may suggest about the future role of oral targeted therapy. Because the therapy affects multiple FGFR family members, the panel also notes the importance of monitoring potential off-target effects.

A second investigational agent, dabogratinib, is also discussed. Designed to more selectively inhibit FGFR3, the therapy is being evaluated in both treatment-naive children and those previously exposed to growth-modulating therapy. The study incorporates body proportionality in addition to annualized growth velocity, reflecting increasing interest in endpoints that capture outcomes beyond height alone. The panel emphasizes that these therapies remain investigational and that their long-term roles will depend on continued evaluation of efficacy, proportionality, durability, and safety.

Our next episode, “Monitoring Treatment Response and Adapting Care in Achondroplasia,” returns to the practical management of children receiving growth-modulating therapy. Panelists will discuss how response is tracked over time, how they approach slower responders, and how treatment may intersect with orthopedic decision-making.