BridgeBio Reports Positive Phase 3 PROPEL 3 Results For Infigratinib In Achondroplasia

BridgeBio Pharma, Inc. announced positive topline results from PROPEL 3, its global Phase 3 pivotal trial evaluating oral infigratinib in children with achondroplasia. PROPEL 3 was a one-year, randomized, double-blind, placebo-controlled study enrolling children aged 3 to under 18 years with open growth plates. The trial assessed the efficacy and safety of infigratinib compared with placebo.

The study met its primary endpoint, demonstrating a statistically significant improvement in annualized height velocity (AHV) versus placebo at Week 52. The least squares (LS) mean treatment difference was +1.74 cm/year (p<0.0001), with a mean treatment difference of +2.10 cm/year. Results across secondary measures were consistent with the primary outcome: Absolute AHV at Week 52 showed significant improvement, with the infigratinib group achieving an LS mean of 5.96 cm/year compared to 4.22 cm/year in the placebo arm, the highest LS mean absolute AHV reported to date in a randomized achondroplasia trial.

"Achondroplasia is a genetic condition driven by FGFR3 that affects more than stature alone, with consequences on physical functioning and independence that can impact widely over a person’s lifetime,” said Ravi Savarirayan, M.D., Ph.D. of Murdoch Children’s Research Institute in Melbourne, Australia, and global lead investigator for PROPEL 3. “Infigratinib is the first oral therapy designed to target FGFR3 and directly address the underlying cause of achondroplasia. In the broadest age range studied to date, oral infigratinib has demonstrated the highest and most significant improvement in annualized growth velocity, along with the first statistically significant improvement in body proportionality, in children aged 3 to 8 years, reported for any therapy approved or in development for this condition. Taken together, these best-in-class results highlight the transformative potential for infigratinib to address aspects of achondroplasia beyond linear height, and with a product administered orally.”

Change from baseline in height Z-score (referenced to the achondroplasia population) was superior to placebo, with an LS mean treatment difference of +0.32 standard deviations (p<0.0001). The treatment arm showed an LS mean improvement of +0.41 SD, the largest improvement observed in a randomized trial in this condition. In a pre-specified exploratory subgroup analysis of children younger than eight years (more than half of participants), infigratinib became the first therapy to demonstrate statistical significance versus placebo in improving upper-to-lower body proportionality in a randomized achondroplasia study. The LS mean decrease versus placebo was -0.05 (p<0.05).

“There remains a significant unmet need for therapeutic options that are effective, practical, and less invasive for children living with achondroplasia,” said Daniela Rogoff, M.D., Chief Medical Officer, Skeletal Dysplasia of BridgeBio. “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. These results represent meaningful progress for those who have been waiting for a better approach, and we look forward to advancing this program towards global submissions. We would like to thank the study participants, their families, investigators, and study staff who trusted us and joined us on this journey.”

In the overall study population, infigratinib achieved an LS mean reduction of -0.05 in proportionality, with a treatment difference of -0.02 compared to placebo at Week 52 (p=0.1849).

Safety Profile of Infigratinib was generally well tolerated, recorded no study drug-related discontinuations, no serious adverse events related to treatment, three cases (4%) of mild, transient, asymptomatic hyperphosphatemia, none requiring dose adjustments, no adverse events linked to FGFR1 or FGFR2 inhibition (such as retinal or corneal effects), no adverse events commonly associated with CNP analogues, including symptomatic hypotension, injection-site reactions, or hypertrichosis.

“Today’s announcement represents another milestone in achondroplasia research and, pending regulatory review, expands available care to include an oral therapeutic option, offering individuals and families additional choice as they consider their healthcare goals and preferences,” said Michael Hughes, Chair of the Biotech Industry Liaison Committee at Little People of America. “BridgeBio’s commitment to engaging with and learning from the dwarfism community reflects a focus on listening to lived experience and recognising diverse priorities in shaping research efforts. Within this context, the observed improvement in body proportionality with one year of treatment in the PROPEL 3 study is an outcome that individuals and families have identified as meaningful, may be relevant to physical function, and continues to be evaluated to understand its broader significance.”

Based on these findings, BridgeBio plans to engage with regulatory authorities to discuss submissions for a New Drug Application (NDA) and a Marketing Authorisation Application (MAA) in the second half of 2026. Infigratinib has received multiple regulatory designations, including Breakthrough Therapy, Orphan Drug (from both the FDA and EMA), Fast Track, and Rare Pediatric Disease Designation.

The company is also advancing development in related skeletal dysplasias. A Phase 3 program for hypochondroplasia is underway, with participants enrolling in an observational run-in period. Additionally, the PROPEL Infant & Toddler trial is ongoing to evaluate infigratinib in newborns to children under three years of age with achondroplasia