BridgeBio's Oral Infigratinib Meets Primary Goal in Phase 3 PROPEL 3 Achondroplasia Trial

BridgeBio Pharma said on February 12 that its oral drug infigratinib met the primary endpoint of PROPEL 3, a Phase 3 pivotal trial in children with achondroplasia, increasing annualized height velocity by 1.74 cm a year more than placebo at Week 52 (p<0.0001), according to the company's topline release. The company plans to file for approval in the U.S. and Europe in the second half of 2026.

Achondroplasia, the most common cause of disproportionate short stature, is caused by an activating variant in the FGFR3 gene. Infigratinib is a tablet designed to target FGFR3. The results are company-reported topline data.

Growth and proportionality results

PROPEL 3 was a one-year, global, randomized, double-blind, placebo-controlled study that assigned children aged 3 to under 18 with open growth plates 2:1 to infigratinib or placebo. Besides the least-squares mean difference of 1.74 cm a year, BridgeBio reported a mean treatment difference of 2.10 cm a year in the change in annualized height velocity. Absolute height velocity at Week 52 was 5.96 cm a year on infigratinib versus 4.22 cm on placebo.

The trial also met its key secondary endpoint of change in height Z-score, measured against an achondroplasia reference population, with a treatment difference of 0.32 standard deviations (p<0.0001), BridgeBio said.

On a second key secondary endpoint, upper-to-lower body proportionality, results differed by age. In the overall population the difference from placebo was -0.02 (p=0.1849). In a prespecified exploratory analysis of children younger than 8, who made up more than half of participants, the difference was -0.05 (p<0.05), which BridgeBio described as the first statistically significant improvement in body proportionality against placebo in a randomized achondroplasia trial.

"In the broadest age range studied to date, oral infigratinib has demonstrated the highest and most significant improvement in annualized growth velocity," said Ravi Savarirayan of Murdoch Children's Research Institute in Melbourne, the trial's global lead investigator, as quoted by PharmaNow.

Safety and next steps

BridgeBio reported no discontinuations or serious adverse events related to the study drug. Three participants (4%) had hyperphosphatemia, all mild, transient and asymptomatic, and none needed a dose change. The company said it saw no adverse events tied to inhibition of the related receptors FGFR1 or FGFR2, such as retinal or corneal effects, and none of the adverse events associated with CNP analogue drugs: symptomatic hypotension, injection-site reactions or hypertrichosis.

BridgeBio said it intends to meet with regulators to discuss submitting a New Drug Application and a Marketing Authorization Application in the second half of 2026. Infigratinib holds FDA Breakthrough Therapy designation for achondroplasia, as well as orphan drug, Fast Track and rare pediatric disease designations.

The company also said it will accelerate development of infigratinib in hypochondroplasia, where it is enrolling an observational run-in for a Phase 3 trial, and continues the PROPEL Infant & Toddler trial in children from birth to under 3.