Fibroblast growth factor receptors or FGFRs, are tyrokine kinase receptors on the surface of cells that link growth factor signalling with the downstream PI3K/AKT and MAPK pathways to regulate cellular proliferation and survival. The FGFR family has four members (encoded by the FGFR1-4 genes).
Overactivity of these pathways are critical contributors to many forms of cancers, most notably cholangiocarcinoma (bile duct cancer) and urothelial carcinoma (bladder cancer). FGFR2 fusions are present in 13% of cholangiocarcinomas, and FGFR3 mutations are present in 64% of non-muscle invasive urothelial carcinomas.
In achondroplasia, activating mutations in FGFR3 suppress proliferation and maturation of growth plate chondrocytes, leading to shortened bones. Complications can be severe, with an increased risk of death during infancy and the potential for compressed bone formation that can lead to nerve compression. Achondroplasia affects one out of every 20,000 live births.
ABOUT INFIGRATINIB (BGJ398)
Infigratinib (BGJ398) is a best-in-class, FGFR-selective, orally-administered investigational new drug in clinical development for the treatment of patients with FGFR-driven cancers. QED Therapeutics acquired the worldwide rights to infigratinib from Novartis for use in all applications and will develop the compound as a treatment for multiple FGFR-driven diseases, including cancers and achondroplasia.
Infigratinib is currently under study in a Phase 2 trial for the treatment of chemotherapy-refractory cholangiocarcinoma (bile duct cancer) with FGFR-fusions. In an early analysis of 63 patients in the ongoing trial, infigratinib demonstrated a 30.2% overall response rate. Of the subset of patients with FGFR2 fusions, there was a 39.6% overall response rate. To date, over 350 patients have been treated with infigratinib in numerous clinical trials. For more information about infigratinib clinical trials, please visit www.clinicaltrials.gov.