Oral Infigratinib Meets Annualized Height Velocity Endpoint in Phase 3 Achondroplasia Trial

BridgeBio Pharma has announced positive topline results from PROPEL 3, a global phase 3 study of oral infigratinib in children living with achondroplasia, showing it met the primary endpoint of change from baseline in annualized height velocity (AHV) at week 52 (P <.0001).1

As described in a February 12, 2026, release from the Company, US Food and Drug Administration (FDA) New Drug Application (NDA) and Marketing Authorization Application (MAA) submissions planned in the second half of 2026 for achondroplasia. Additionally, given the strength of the PROPEL 3 data, BridgeBio plans to accelerate the development of oral infigratinib in hypochondroplasia, and is enrolling the observational run-in for the phase 3 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,” Ravi Savarirayan, MD, PhD, of Murdoch Children’s Research Institute in Melbourne, Australia, and global lead investigator for PROPEL 3, said in a statement. “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.”

Oral infigratinib is the only therapeutic option in development for achondroplasia to have Breakthrough Therapy Designation from the FDA. The September 2024 designation was supported by preliminary clinical evidence from the PROPEL 2 clinical trial, meeting the FDA’s requirement of potentially demonstrating substantial improvement in efficacy over available therapies on clinically significant endpoint(s). In Cohort 5 of the study (0.25 mg/kg/day), oral treatment with infigratinib resulted in a statistically significant and sustained increase in AHV, with a mean change from baseline of +2.51cm/yr at month 12, and +2.50 cm/yr at month 18 (P = .0015) and statistically significant improvement in body proportionality at month 18 (P = .001).2

PROPEL 3 was a global, one-year, 2:1 randomized, double-blinded placebo-controlled clinical study assessing the efficacy and safety of infigratinib in children with achondroplasia aged 3 to <18 years with open growth plates. Through week 52, the study met its primary endpoint for change from baseline in AHV superior to placebo, with an LS mean treatment difference of +1.74 cm/year (P <.0001) and a mean treatment difference of +2.10 cm/year.

Consistent with the primary endpoint, the secondary endpoint of absolute AHV at week 52 showed a significant improvement with infigratinib compared to placebo, with the infigratinib arm achieving the greatest LS mean absolute AHV reported to date in a randomized trial in achondroplasia (5.96 cm/year vs 4.22 cm/year on placebo). Change from baseline in height Z-score (achondroplasia reference population) was also superior to placebo, with an LS mean treatment difference of +0.32 SD (P <.0001), the largest difference observed in a randomized trial in achondroplasia; the LS mean change from baseline on the treatment arm was +0.41 SD, the largest improvement observed on a treatment arm in a randomized trial for achondroplasia.

In a pre-specified exploratory analysis in children younger than 8 years of age of the key secondary endpoint of change from baseline in upper-to-lower body proportionality at week 52, oral infigratinib is the first therapeutic option to show statistical significance against placebo in a randomized trial for achondroplasia, demonstrating an LS mean decrease of -0.05 against placebo (P <.05). In the overall population, infigratinib achieved an LS mean decrease of -0.05, the largest reduction observed in a treatment arm in a randomized achondroplasia trial, with a favorable LS treatment difference of -0.02 versus placebo at week 52 (P = .1849).

In the study, infigratinib was well-tolerated, with no discontinuations related to the study drug and no serious adverse events related to the study drug. A total of 3 cases (4%) of hyperphosphatemia were reported and were all mild, transient, asymptomatic, and not requiring dose reductions or discontinuations. No adverse events associated with inhibition of FGFR1 or FGFR2 were observed, nor were adverse events associated with CNP analogues: symptomatic hypotension, injection site reactions, or hypertrichosis.

Based on these data, BridgeBio described plans to meet with regulatory authorities to discuss plans for submission of a NDA and MAA for infigratinib in the second half of 2026 to support approval. The Company also intends to accelerate the development of infigratinib for hypochondroplasia, and is enrolling participants in the observational run-in for the phase 3 trial. BridgeBio also has an ongoing clinical trial of infigratinib for the newborn to <3 year old age groups in achondroplasia in the PROPEL Infant & Toddler trial.

“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,” Michael Hughes, Chair of the Biotech Industry Liaison Committee at Little People of America, said in a statement. “BridgeBio’s commitment to engaging with and learning from the dwarfism community reflects a focus on listening to lived experience and recognizing 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.”

References

1. BridgeBio Reports Positive Phase 3 Topline Results for Oral Infigratinib with the First Statistically Significant Improvements in Body Proportionality in Achondroplasia. BridgeBio. February 12, 2026. Accessed February 12, 2026. https://investor.bridgebio.com/news/news-details/2026/BridgeBio-Reports-Positive-Phase-3-Topline-Results-for-Oral-Infigratinib-with-the-First-Statistically-Significant-Improvements-in-Body-Proportionality-in-Achondroplasia/default.aspx

2. BridgeBio. bridgebio announces infigratinib is the first ever investigational therapeutic option for achondroplasia to be awarded breakthrough therapy designation by the fda. September 17, 2027. Accessed February 12, 2026. https://investor.bridgebio.com/news/news-details/2024/bridgebio-announces-infigratinib-is-the-first-ever-investigational-therapeutic-option-for-achondroplasia-to-be-awarded-breakthrough-therapy-designation-by-the-fda-09-17-2024/default.aspx