Infigratinib Shows Promise in Phase 2 Trial for Achondroplasia
核心洞察
Infigratinib, an oral FGFR3 (搜索) inhibitor, significantly increased annualized height velocity in children with achondroplasia (搜索) in a Phase 2 trial.
The study demonstrated a mean change from baseline in AHV of +2.50 cm/year at Month 18 with a daily dose of 0.25 mg/kg (P=0.001).
Infigratinib was well-tolerated, with no serious adverse events or negative changes in bone mineral density observed during the trial.
BridgeBio Pharma announced the publication of positive 18-month results from the PROPEL 2 Phase 2 trial of infigratinib in children with achondroplasia (搜索) in the New England Journal of Medicine. The data, also presented at the European Society for Paediatric Endocrinology (ESPE) Meeting, highlight the potential of infigratinib as a first-in-class oral treatment option for this genetic condition.
Significant Height Velocity Increase
The PROPEL 2 trial evaluated infigratinib, an investigational oral small molecule designed to inhibit FGFR3 (搜索) signaling, in children with achondroplasia (搜索). Cohort 5, receiving a daily dose of 0.25 mg/kg, showed a statistically significant increase in annualized height velocity (AHV), with a mean change from baseline of +2.50 cm/year at Month 18 (P=0.001). Additionally, the mean change from baseline in height Z-score was +0.54 (P<0.001) relative to an untreated achondroplasia population at Month 18.
Improved Body Proportionality
The study also demonstrated a statistically significant improvement in body proportionality, with a mean upper to lower body segment ratio of -0.12 (P=0.001) at Month 18. These findings suggest that infigratinib not only increases height but also improves overall body structure in children with achondroplasia (搜索).
Safety and Tolerability
Infigratinib was well-tolerated in the trial, with no serious adverse events (SAE) or treatment-emergent adverse events (TEAEs) leading to treatment discontinuation. Furthermore, there was no accelerated progression of bone age, negative changes in bone mineral density, or other bone-related adverse events observed.
Expert Commentary
"Publication of results from PROPEL 2 in the New England Journal of Medicine and Breakthrough Therapy Designation of infigratinib by the FDA underscore the significance and importance of these data and the potential of this oral therapy to not only increase height, but more importantly, enhance functionality for children with achondroplasia (搜索)," said Ravi Savarirayan, M.D., Ph.D., of Murdoch Children's Research Institute in Melbourne, Australia, the global lead investigator for PROPEL 2 and lead author of the NEJM publication.
Ongoing Phase 3 Trial
BridgeBio is continuing to evaluate infigratinib in PROPEL 3, a global Phase 3 registrational study in achondroplasia (搜索), with enrollment completion anticipated by the end of 2024. Infigratinib has received Breakthrough Therapy Designation, Orphan Drug Designation, Fast Track Designation, and Rare Pediatric Disease Designation from the FDA for achondroplasia.