BridgeBio's Oral Infigratinib Shows Benefits Beyond Growth in Phase 3 PROPEL 3 Achondroplasia Trial
核心洞察
Oral infigratinib produced favorable trends versus placebo on exploratory endpoints including sleep apnea, otitis media (搜索) and body composition at 52 weeks in the Phase 3 PROPEL 3 trial.
Mean total apnea-hypopnea index rose 10.4% with infigratinib versus 49.2% with placebo, and was unchanged in children younger than 8 years.
Annualized otitis media (搜索) event rates were 38% lower overall and 47% lower in children under 8 years compared with placebo.
BridgeBio Pharma has presented new exploratory analyses from PROPEL 3, its global Phase 3 pivotal study of oral infigratinib in children living with achondroplasia (搜索), showing directionally favorable trends beyond growth across medical complications associated with the condition, including sleep apnea, otitis media (搜索) and body composition. The data were presented at the Annual European Society for Paediatric Endocrinology (ESPE) Meeting 2026 in Marseille, France, in a late-breaking oral presentation by Julie Hoover-Fong, M.D., Ph.D. of Johns Hopkins University.
The findings build on the previously reported PROPEL 3 primary and secondary endpoint results published in the New England Journal of Medicine, in which oral infigratinib demonstrated a +2.10 cm/year improvement in annualized height velocity (AHV) versus placebo (p<0.0001) and a statistically significant improvement in body proportionality within 52 weeks in children younger than 8 years of age.
Sleep Apnea Measures Stabilize at 52 Weeks
In the exploratory analysis, the mean total apnea-hypopnea index (AHI) at 52 weeks remained consistent with the baseline mean in the oral infigratinib group, with a 10.4% increase, versus a 49.2% increase in the placebo group. Among children younger than 8 years of age, the mean total AHI at 52 weeks was unchanged for the oral infigratinib group, versus a 63.2% increase for the placebo group.
Lower Rates of Otitis Media
The estimated annualized rate of otitis media (搜索) events — a recurrent complication in children with achondroplasia (搜索) that can affect hearing and speech development — was 38% lower in the oral infigratinib group compared to placebo. In children younger than 8 years of age, the annualized rate was 47% lower with oral infigratinib compared to placebo.
Body Composition Shifts Favor Treatment
Mean change from baseline in body mass index was smaller in the oral infigratinib group compared to placebo (0.50 versus 0.93 kg/m2). The treatment group also showed a greater increase in lean body mass (1.77 versus 1.58 kg) and smaller increases in body fat mass (0.95 versus 1.12 kg) and visceral fat volume (1.55 versus 18.42 mL) compared to placebo.
Three-Year Growth and Proportionality Data
In addition to the late-breaking oral presentation, BridgeBio shared a poster, "Longer-Term Efficacy and Safety Results of Infigratinib in Children with Achondroplasia (搜索)," presented by Dr. Irving. In children treated for up to three years in the PROPEL program, oral infigratinib demonstrated sustained improvements in growth, with a change from baseline in height Z-score relative to the achondroplasia population of +0.92 SD at Year 3, and sustained improvements in proportionality, with a change from baseline in upper-to-lower body segment ratio of -0.15 at Year 3. Oral infigratinib continued to be well-tolerated, with no new safety signals identified.
"In the past, achondroplasia (搜索) research has focused largely on measuring growth because height can be readily determined. But families have consistently emphasized that their priorities extend well beyond the growth chart," said Melita Irving, M.D. of Guy's and St Thomas' NHS Foundation Trust, London, UK. "Growth is only one part of the picture of this medically complicated condition in which children experience disrupted sleep, recurring ear infections, or other health challenges associated with achondroplasia. What I find especially encouraging here is not only the consistent benefit observed across each measure, but that the longer-term data from the PROPEL program show improvements in growth and body proportionality sustained through three years of treatment, and a safety profile that remained favorable with no new safety signals identified."
BridgeBio also shared one poster focused on PROPEL Infant & Toddler (I&T), an ongoing Phase 2/2b study in children under 3 years old with achondroplasia (搜索), and one eposter focused on qualitative research on the impacts of hypochondroplasia (搜索).
Regulatory Path and Mechanism
PROPEL 3 demonstrated best-in-class improvements in annualized height velocity and, for the first time in a Phase 3 achondroplasia (搜索) study, statistically significant improvements in body proportionality and arm span, supporting its potential as the first oral targeted therapeutic option that directly impacts FGFR3 (搜索). The topline results were published as an original research article in NEJM and simultaneously presented at the International Congress of Children's Bone Health (ICCBH) 2026 in a late-breaking oral presentation.
BridgeBio believes oral infigratinib is positioned to become the first and only approved oral therapy and a potential best-in-class option for children living with achondroplasia (搜索). The company submitted a New Drug Application to the FDA for oral infigratinib in achondroplasia and anticipates a U.S. launch in mid-2027. BridgeBio intends to submit a Marketing Authorization Application for achondroplasia to the European Medicines Agency in the fourth quarter of 2026.
Oral infigratinib has received Breakthrough Therapy Designation from the FDA based on shared results from the PROPEL 2 clinical trial, which meet the agency's requirement of potentially demonstrating substantial improvement in efficacy over available therapies on clinically significant endpoints. It has also received Orphan Drug Designation, Fast Track Designation and Rare Pediatric Disease Designation for achondroplasia (搜索) from the FDA. If approved, BridgeBio may qualify for a Priority Review Voucher.
Disease Burden and Mechanism of Action
Achondroplasia (搜索) is the most common cause of disproportionate short stature, affecting approximately 55,000 people in the U.S. and European Union, including up to 10,000 children and adolescents with open growth plates. The condition can be associated with medical complications such as obstructive sleep apnea (搜索), middle ear dysfunction, kyphosis and spinal stenosis, which may impact overall health and wellbeing. It is uniformly caused by an activating variant in FGFR3 (搜索).
Oral infigratinib is an investigational small molecule designed to inhibit FGFR3 (搜索) signaling and target skeletal dysplasias, including achondroplasia (搜索) and hypochondroplasia (搜索), at their source. Overactivating FGFR3 pathogenic variants drive downstream MAPK and STAT1 signaling that aberrates growth plate development, thereby causing disproportionate short stature and the potential for serious health complications. Oral infigratinib improves bone growth by decreasing the overactivity of FGFR3.
BridgeBio said it is committed to exploring the potential of oral infigratinib on wider medical and functional impacts of achondroplasia (搜索), hypochondroplasia (搜索) and other skeletal dysplasia conditions. Information about the PROPEL I&T trial (NCT07169279), the ACCEL observational lead-in study in hypochondroplasia (NCT06410976) and the ACCEL 2/3 Phase 2/3 study in hypochondroplasia (NCT06873035) is available on clinicaltrials.gov.