Oral medication boosts growth in children with achondroplasia
Children with achondroplasia grew 1.74 cm more per year when treated with the oral medication infigratinib compared to those receiving a placebo, according to a clinical trial. The PROPEL 3 study, published June 28, 2026, in The New England Journal of Medicine, tracked 114 patients to evaluate the drug as a potential treatment for the most common form of skeletal dysplasia.
Targeting the root of skeletal impairment
Achondroplasia stems from pathogenic variants in the FGFR3 gene. These variants trigger the overactivation of MAPK and STAT1 signaling pathways, which disrupts endochondral ossification. Infigratinib operates as an oral, selective tyrosine kinase inhibitor. By blocking the phosphorylation of FGFR3, the drug acts upstream of the MAPK cascade. This sets it apart from existing therapies like vosoritide and navepegritide, which are C-type natriuretic peptide analogs that target only the MAPK pathway and require subcutaneous administration.
Growth velocity and trial outcomes
The randomized, double-blind, placebo-controlled PROPEL 3 trial spanned 27 centers across 10 countries. Researchers assigned 114 children, aged 3 to 17, to two groups: 75 received 0.25 mg/kg/day of infigratinib, while 39 received a placebo.
The primary endpoint—annual growth velocity—yielded statistically significant results. The treatment group grew at an average rate of 5.96 cm per year, versus 4.22 cm for the placebo group, a difference of 1.74 cm/year (95% CI, 1.31–2.17; p < 0.001). Height z-scores also improved, showing a difference of +0.32 (95% CI, 0.23–0.41; p < 0.001) over the placebo.
While global body proportions showed no significant improvement at 52 weeks, researchers observed more favorable effects in children aged 3 to 8, a period where disproportions are most likely to evolve.
Shifting the treatment burden
The efficacy found in PROPEL 3 mirrors data from the vosoritide trial (study 111-301), which showed an adjusted difference of 1.57 cm/year. Direct comparisons remain difficult due to varying inclusion criteria and data handling methods. However, infigratinib’s oral delivery offers an argument as a potential alternative to injectable therapies.
Safety profile and monitoring
At the 0.25 mg/kg/day dose, the safety profile was favorable. Adverse events affected 96% of the infigratinib group and 95% of the placebo group, with most cases classified as mild or moderate. There were no deaths and no treatment-related serious adverse events.
Investigators monitored closely for side effects associated with broader FGFR1-3 inhibition. They observed no instances of retinal or corneal toxicity. While three patients experienced transient, asymptomatic elevations in phosphate levels, these resolved without recurrence. Throughout the 52-week study, researchers detected no impact on bone mineral density or bone age.
Regulatory path and ongoing research
Infigratinib is not yet available on the French market. Future regulatory decisions will likely hinge on the PROPEL OLE (Open-Label Extension) study, which is gathering long-term data on quality of life and adult height. Separately, the “PROPEL Infant and Toddler” Phase 2/2b trial is currently testing the drug in children under the age of 3.
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