BridgeBio Reports Phase 3 Data for Oral Infigratinib in Achondroplasia, Claiming First Statistically Significant Improvement in Body Proportionality
BridgeBio Pharma announced positive topline results from PROPEL 3, a global Phase III pivotal study evaluating oral infigratinib in children with achondroplasia, with the trial meeting its primary endpoint of change from baseline in annualized height velocity at Week 52 (p<0.0001). Infigratinib is a selective FGFR tyrosine kinase inhibitor, originally developed by Novartis and licensed to BridgeBio's subsidiary QED Therapeutics, that directly targets the overactive FGFR3 signaling uniformly responsible for achondroplasia. The readout carries particular weight for BridgeBio because infigratinib represents the only oral therapeutic candidate in advanced clinical development for the condition and the only one to hold Breakthrough Therapy Designation from the US FDA for this indication. If confirmed through regulatory review, the PROPEL 3 Phase III results would position BridgeBio infigratinib as a direct competitor to BioMarin's injectable vosoritide (Voxzogo), which has been the sole approved pharmacotherapy for achondroplasia since 2021.
Trial specifics: PROPEL 3 Phase III results in achondroplasia
PROPEL 3 was a global, one-year, double-blind, placebo-controlled study with 2:1 randomization (infigratinib to placebo) in children aged 3 to under 18 years with open growth plates — the broadest age range studied to date in a randomized trial for this condition. The primary endpoint was change from baseline in annualized height velocity (AHV) at Week 52. Infigratinib demonstrated superiority over placebo with a least-squares (LS) mean treatment difference of +1.74 cm/year and a mean treatment difference of +2.10 cm/year (p<0.0001). The absolute AHV on the infigratinib arm reached 5.96 cm/year versus 4.22 cm/year on placebo, which the company described as the highest LS mean absolute AHV reported in a randomized achondroplasia trial.
Among secondary endpoints, the change from baseline in height Z-score (using an achondroplasia reference population) was also superior to placebo, with an LS mean treatment difference of +0.32 SD (p<0.0001) and an LS mean increase of +0.41 SD on the treatment arm. In a pre-specified exploratory analysis of body proportionality in achondroplasia — specifically change from baseline in upper-to-lower body ratio at Week 52 among children younger than 8 years, who comprised more than 50% of participants — oral infigratinib achieved an LS mean decrease of -0.05 versus placebo (p<0.05). The company stated this represents the first statistically significant improvement in body proportionality against placebo reported for any therapy, approved or in development, for achondroplasia. In the overall study population, the proportionality result was directionally consistent (LS treatment difference of -0.02 versus placebo) but did not reach statistical significance (p=0.1849).
Safety data were clean by the standards of a pediatric chronic-use program. There were no discontinuations or serious adverse events related to study drug. Three cases (4%) of hyperphosphatemia were reported, all described as mild, transient, and asymptomatic, with none requiring dose reduction or discontinuation. No adverse events associated with FGFR1 or FGFR2 inhibition (such as retinal or corneal effects) were observed, nor were there adverse events characteristic of CNP analogues, including symptomatic hypotension, injection site reactions, or hypertrichosis.
Based on the infigratinib Phase III topline results, BridgeBio said it intends to meet with regulatory authorities and plans to submit a New Drug Application to the US FDA and a Marketing Authorization Application to the EMA in the second half of 2026. "The PROPEL 3 data support the potential of an oral medicine directly targeting FGFR3 overactivity to address important clinical needs, while fitting into daily life for families who are seeking a non-injectable option," said Daniela Rogoff, Chief Medical Officer, Skeletal Dysplasia, at BridgeBio. The company also said it plans to accelerate development of infigratinib for hypochondroplasia, a related skeletal dysplasia, and is enrolling participants in the observational run-in (NCT06410976) for a Phase II/III trial in that indication. A separate trial in infants and toddlers (newborn to under 3 years) with achondroplasia, PROPEL Infant & Toddler, is also ongoing.
Oral achondroplasia treatment: mechanism and regulatory context
Achondroplasia affects approximately 55,000 people in the US and EU and is uniformly caused by an activating variant in the FGFR3 gene. The resulting overactive FGFR3 signaling suppresses chondrocyte proliferation and differentiation in the growth plate, restricting endochondral bone growth and producing disproportionate short stature along with complications including obstructive sleep apnea, kyphosis, and spinal stenosis. Infigratinib acts at the receptor level, directly inhibiting FGFR3 tyrosine kinase activity — a mechanism distinct from the downstream CNP/NPR-B/cGMP pathway targeted by vosoritide. Preclinical work in achondroplasia mouse models demonstrated that low-dose infigratinib improved long-bone growth and growth plate organization, supporting the rationale for clinical development at doses substantially lower than those used in the drug's prior oncology program.