Preventing height impairment and its complications

SAN FRANCISCO—BridgeBio Pharma Inc. recently noted that its affiliate QED Therapeutics has dosed it first child with achondroplasia with the investigational medicine infigratinib, an orally available small molecule that targets the overactivity of fibroblast growth factor receptor 3 (FGFR3) in its PROPEL 2 Phase 2 clinical trial. Achondroplasia is the most common cause of disproportionate short stature.

“With preclinical evidence showing increased growth in the long bones, spine and cranial bones, including the base of the skull, there is the potential for infigratinib to help children with achondroplasia by decreasing the impact of serious medical complications,” said Dr. Ravi Savarirayan, a clinical geneticist and group leader of skeletal biology and disease at Murdoch Children’s Research Institute in Australia—as well as the lead investigator for the PROPEL 2 trial. “Additionally, infigratinib is being studied as a once-daily dose taken orally, which is an important factor for administration of therapies to children with achondroplasia.”

Achondroplasia is caused by an alteration in the FGFR3 gene, which causes the FGFR3 protein to be overly active. This interferes with skeletal development and can lead to disturbances in bone growth. Infigratinib is an oral investigational medicine that is designed to reduce the activity of FGFR3.

“The start of this clinical trial is the culmination of more than two years of work—first to secure rights to develop infigratinib, which we pursued following the publication of data relating to its potential in achondroplasia, and then to establish preclinical data showing the efficacy and safety of very low doses of the molecule,” said Dr. Michael Henderson, CEO of QED Therapeutics. “Infigratinib illustrates the heart of what BridgeBio set out to do: leverage the highest quality science to identify and develop potential therapies that target genetically driven conditions at their source. Our hope is that a daily, oral dose of infigratinib, which directly targets FGFR3, can provide health benefits for children with achondroplasia.”

The PROPEL 2 trial is a Phase 2 dose escalation and dose expansion trial and the first clinical trial to study infigratinib at low doses in children with achondroplasia. The goal of the study is to assess safety and measure changes from baseline in annualized height velocity and changes in other health factors. To be eligible for the trial, children must first complete a six-month period of assessment in the PROPEL prospective clinical assessment study.