In a multinational dose-finding study, the FGFR1–3–selective tyrosine kinase inhibitor infigratinib demonstrated acceptable safety and meaningful growth benefits, particularly at the highest dose tested. Importantly, no child discontinued treatment because of adverse events.

Safety Profile Remained Manageable

The trial enrolled 72 children ages 3 to 11 years with genetically confirmed achondroplasia across 19 centers in North America, Europe, and Australia. All participants experienced at least one adverse event during treatment, but the vast majority were mild or moderate in severity. Serious (grade 3) events were uncommon and varied across dose groups, with no clear treatment-limiting safety signal.

Only seven children experienced side effects considered possibly related to infigratinib, and all were mild. These included gastrointestinal symptoms, changes in vitamin D levels, reduced appetite, and transient laboratory abnormalities such as elevated phosphate levels.

Dose-Dependent Growth Gains Observed

Efficacy findings were most pronounced in children receiving the highest dose, 0.25 mg/kg daily. In this group, annualized height velocity increased consistently and was sustained through 18 months of therapy.

At the end of follow-up, children in the highest-dose cohort showed an average increase in growth rate of approximately 2.5 cm per year above baseline, along with meaningful improvements in height-for-age z scores compared with an untreated achondroplasia reference population. Improvements in body proportionality were also observed, reflected by a reduction in the upper-to-lower body segment ratio.

Overall, most children in this cohort experienced growth acceleration, with many achieving increases of at least 25% above baseline growth rates.

Potential Advantages Over Existing Therapy

Currently, vosoritide is the only approved pharmacologic treatment for pediatric achondroplasia and requires daily subcutaneous injections. Investigators emphasized that an effective oral option could meaningfully reduce treatment burden for children and families.

“The convenience of oral administration, combined with comparable effects on height and body proportionality, could have important practical implications—particularly in settings where daily injections are challenging,” lead investigator Ravi Savarirayan, MBBS, MD, said in a statement.

A Repurposed Drug Finds New Direction

Infigratinib’s path to development has been unconventional. The FGFR inhibitor previously received accelerated FDA approval in 2022 for cholangiocarcinoma under the name Truseltiq, though that indication was later withdrawn. Its targeted mechanism, however, aligns with the FGFR3-driven biology of achondroplasia, providing a strong scientific rationale for pediatric use.

Next Steps: Phase III Evaluation

While the study was limited by relatively small numbers at each dose level, the overall safety and efficacy signals supported advancement to late-stage testing. A global phase III, randomized, placebo-controlled trial is now underway, aiming to enroll approximately 110 children and adolescents with growth potential.

If confirmed, these results could expand treatment options for a lifelong genetic condition associated with disproportionate short stature and multiple orthopedic and neurologic complications—potentially improving not just height outcomes, but long-term function and independence for affected children.