BridgeBio (BBIO) Study result summary

Study design and population

• 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 74 in the treatment arm and 39 in placebo.

• The study assessed endpoints including annualized height velocity (AHV), height Z-score, and body proportionality.

• Treatment lasted 52 weeks, with an option to enter a long-term extension study.

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 seen in any achondroplasia RCT.

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

• Height Z-score improved by +0.41 in the treatment arm and LS mean difference vs placebo was +0.32 (p<0.0001), both the highest reported to date.

• Statistically significant improvement in body proportionality (upper-to-lower segment ratio) was observed in children aged 3–8 years (LS mean difference -0.05, p<0.05).

• Subgroup analyses showed consistent efficacy across all age groups studied.

Safety and tolerability

• Infigratinib was well-tolerated, with no serious adverse events or discontinuations related to the drug.

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

• No adverse events related to FGFR1/2 inhibition or typical CNP analog side effects were observed.

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