Infigratinib Shows Promise in Phase 2 Trial for Children with Achondroplasia
核心洞察
Infigratinib significantly increased annualized height velocity in children with achondroplasia (搜索) in a Phase 2 trial, as published in _The New England Journal of Medicine_.
The study also demonstrated a positive change in height Z-score and improved body proportionality with infigratinib treatment over 18 months.
Oral infigratinib was well-tolerated, with no serious adverse events leading to treatment discontinuation in the studied pediatric population.
BridgeBio Pharma's infigratinib, an investigational therapy, has demonstrated positive results in a Phase 2 clinical trial (PROPEL 2) involving children with achondroplasia (搜索). The study, published in The New England Journal of Medicine, revealed statistically significant and sustained increases in annualized height velocity (AHV), positive changes in height Z-score, and improved body proportionality. These findings suggest that infigratinib could address the unmet medical needs of children with this genetic skeletal condition.
The PROPEL 2 study (NCT04265651) evaluated the safety and efficacy of infigratinib, an oral bioavailable FGFR1 (搜索)-3 selective tyrosine kinase inhibitor, in 72 children aged 3 to 11 years with achondroplasia (搜索). Participants were divided into five cohorts, each receiving a different daily dose of infigratinib (0.016 to 0.25 mg/kg) for six months, followed by an extended 12-month treatment period. The primary efficacy outcome was the change from baseline in AHV, while the primary safety outcome was the incidence of adverse events (AEs) leading to dose reduction or discontinuation.
The results showed a notable increase in AHV in cohort 5 (0.25 mg/kg), which persisted throughout the study, with a mean change from baseline at 18 months of 2.50 cm per year (95% CI, 1.22 to 3.79; P = 0.001). Furthermore, infigratinib treatment in cohort 5 led to a mean change from baseline in height Z-score of +0.54 (P < 0.001) compared to an untreated achondroplasia (搜索) population at 18 months. There was also a statistically significant improvement in body proportionality, with a mean upper to lower body segment ratio of –0.12 (P = 0.001) at 18 months.
The safety profile of infigratinib was favorable, with no serious adverse events (SAEs) or treatment-emergent adverse events (TEAEs) leading to discontinuation. All children experienced at least one adverse event during treatment, but most were mild to moderate in severity.
According to Ravi Savarirayan, MD, PhD, the global lead investigator for PROPEL 2, the data and Breakthrough Therapy Designation from the FDA highlight the potential of infigratinib to increase height and enhance functionality for children with achondroplasia (搜索). Melita Irving, MD, an investigator for the infigratinib clinical program, noted the absence of safety signals and adverse changes in bone age or bone mineral density, expressing optimism for further evaluation in the ongoing Phase 3 trial (PROPEL 3) and the Phase 2 portion of the ACCEL program in children with hypochondroplasia (搜索).
BridgeBio Pharma anticipates completing enrollment for the PROPEL 3 study by the end of 2024. In addition to Breakthrough Therapy Designation, infigratinib has received Orphan Drug Designation, Fast Track Designation, and Rare Pediatric Disease Designation from the FDA.