BridgeBio (BBIO) Conference presentation summary

Disease background and study rationale

• Achondroplasia is caused by FGFR3 gene mutations, leading to impaired bone growth and disproportionate short stature, with a global prevalence of about 250,000 individuals.

• Clinical features include short stature, macrocephaly, midface hypoplasia, spine curvature, and leg bowing, often resulting in lifelong physical and psychosocial challenges.

• Infigratinib is an oral FGFR1-3 selective tyrosine kinase inhibitor designed to target FGFR3 overactivity, the underlying cause of achondroplasia.

Study design and participant characteristics

• PROPEL 3 is a randomized, double-blind, placebo-controlled Phase 3 trial in children aged 3 to <18 years with genetically confirmed achondroplasia.

• 114 children were randomized (74 to infigratinib, 39 to placebo) for a 52-week treatment period, with primary and secondary endpoints focused on growth and body proportions.

• Baseline characteristics were balanced between groups, with a mean age of about 7.9 years and a diverse racial distribution.

Efficacy outcomes

• Infigratinib significantly increased annualized height velocity at week 52 compared to placebo (mean difference 2.10 cm/year, p<0.0001).

• Height velocity in the treatment group approached that of average stature children.

• Significant improvement in height z-score was observed (mean difference 0.32, p<0.0001).

• A trend toward improved upper-to-lower body segment ratio was seen, reaching significance in children aged 3 to <8 years.

• Arm span z-score also improved significantly, supporting positive effects on body proportions.