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, with 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 to enter a long-term extension.

• Baseline characteristics were well balanced between arms, ensuring comparability.

• The primary endpoint was change from baseline 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 +2.10 cm/year and LS mean difference of +1.74 cm/year vs placebo at week 52 (p<0.0001), the largest difference seen in any RCT for achondroplasia.

• The treatment arm reached a mean AHV of 5.96 cm/year, matching average-stature pediatric populations and representing the largest LS mean absolute AHV reported to date.

• Significant improvement in height Z-score, with LS mean increase of +0.41 SD on treatment arm and +0.32 LS mean difference vs placebo, both the highest reported to date.

• Statistically significant improvement in body proportionality was observed in children aged 3–8 years (LS mean difference -0.05, p<0.05), a first for a 1-year trial.

• Efficacy was consistent across all age groups studied.

Safety and tolerability

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

• Most adverse events were mild or moderate and balanced between arms; three cases of mild, transient hyperphosphatemia occurred, none requiring dose adjustment.

• No adverse events associated with CNP analogs or FGFR1/2 inhibition were observed.

• Phosphorus levels remained within normal ranges throughout the study.