BridgeBio (BBIO) Study result summary

Study background and design

• PROPEL-3 was a global, randomized, double-blind, placebo-controlled phase III trial in 113 children aged 3 to <18 years with achondroplasia, evaluating oral infigratinib 0.25 mg/kg/day versus placebo over 52 weeks, the largest age range in any RCT for this condition.

• Participants were randomized 2:1 to infigratinib or placebo after at least 6 months in an observational study, with an option for long-term extension.

• The primary endpoint was change in annualized height velocity (AHV) at week 52; key secondary endpoints included change in height Z-score and body proportionality.

Efficacy results

• Infigratinib achieved a mean difference in AHV of 2.1 cm/year and an LS mean difference of 1.74 cm/year vs. placebo at week 52 (p<0.0001), the largest seen in any RCT for achondroplasia.

• The treatment arm reached a mean AHV of 5.96 cm/year, matching average-stature pediatric populations.

• Statistically significant improvements were observed in height Z-score (LS mean increase of 0.41 SD, p<0.0001) and body proportionality (LS mean difference -0.05, p<0.05) in children under 8 years.

• Efficacy was consistent across all age groups studied.

Safety and tolerability

• Infigratinib was well-tolerated, with no serious adverse events, no discontinuations related to the drug, and no safety signals for FGFR1/2 inhibition.

• Most adverse events were mild or moderate and balanced between arms; three cases of mild, transient hyperphosphatemia occurred, all resolving without intervention.

• Mean serum phosphate levels remained within normal ranges throughout the study.