Infigratinib Exposure Did Not Inhibit FGFR1 Signaling in Human Adipocytes
An abstract presented at the American Society for Bone & Mineral Research (ASBMR) 2026 Annual Meeting reports that infigratinib concentrations corresponding to clinically relevant plasma exposures did not inhibit FGF21-mediated FGFR1 signaling in primary human adipocytes. The laboratory findings confirm the safety observations reported in children receiving infigratinib for achondroplasia.
The authors cited results from the phase 3 PROPEL 3 trial, which included children aged 3 years to younger than 18 years with achondroplasia. The results showed that oral infigratinib, 0.25 mg/kg/d, significantly increased annualized height velocity and height z-score compared with placebo. They also cited no clinically meaningful evidence of FGFR1-associated safety concerns, such as hyperphosphatemia.
To build on these results and further examine whether drug concentrations achieved at that dose inhibit FGFR1 signaling, the investigators differentiated primary human adipocytes and characterized them using adipocyte-specific gene expression and Oil Red O staining. They measured expression of FGFR1 through FGFR4; FGFR1 expression was substantially higher than expression of the other 3 receptors.
The investigators then incubated the cells for 2 hours with a vehicle control or infigratinib concentrations ranging from 0.125 to 30 nM. They stimulated the cells with 10 nM FGF21 and assessed FGFR1 signaling by measuring phosphorylated ERK relative to total ERK. Concentrations corresponding to clinically relevant unbound peak and average plasma exposures did not inhibit FGF21-mediated signaling in this assay.
“ These results provide supportive mechanistic evidence that plasma concentrations of infigratinib achieved with 0.25 mg/kg/day dosing do not meaningfully inhibit FGF21-mediated FGFR1 signaling in primary human adipocytes,” the researchers wrote. “Our findings are consistent with the absence of clinically meaningful FGFR1-related safety events (eg, hyperphosphatemia) observed in the PROPEL 3 trial.”
Reference
Huang E, Ding J, Choi T, Ge XS, Shah B. Lack of peripheral FGFR1 inhibition at clinically relevant infigratinib exposures supports the safety profile observed in children with achondroplasia. Abstract presented at: American Society for Bone & Mineral Research 2026 Annual Meeting; October 9-12, 2026; Boston, MA. Accessed October 7, 2026. https://eppro01.ativ.me/web/page.php?page=Session&project=ASBMR26&id=p8682-397