BridgeBio's Oral Infigratinib Achieves Breakthrough Results in Phase 3 Achondroplasia Trial
核心洞察
BridgeBio's PROPEL 3 trial met its primary endpoint, showing oral infigratinib significantly improved annualized height velocity by 1.74 cm/year compared to placebo in children with achondroplasia (搜索).
The study achieved the first statistically significant improvement in body proportionality for any achondroplasia (搜索) therapy, with a meaningful reduction in upper-to-lower body ratio in children under 8 years.
Infigratinib demonstrated excellent safety with no drug-related discontinuations or serious adverse events, positioning it as the first oral FGFR3 (搜索)-targeted therapy for this genetic condition.
BridgeBio Pharma announced positive topline results from PROPEL 3, its global Phase 3 pivotal study of oral infigratinib in children with achondroplasia (搜索), marking a significant advancement in treating this genetic condition. The study successfully met its primary endpoint of change from baseline in annualized height velocity (AHV) at Week 52 with statistical significance (p<0.0001).
The trial demonstrated a mean treatment difference of +2.10 cm/year against placebo, with an LS mean of +1.74 cm/year. This represents the highest and most significant improvement in annualized growth velocity reported for any therapy approved or in development for achondroplasia (搜索), according to global lead investigator Ravi Savarirayan, M.D., Ph.D. of Murdoch Children's Research Institute in Melbourne, Australia.
Historic Achievement in Body Proportionality
In a groundbreaking development, oral infigratinib became the first therapeutic option to demonstrate statistically significant improvement in body proportionality against placebo in a randomized achondroplasia (搜索) trial. The pre-specified exploratory analysis in children younger than 8 years (representing more than 50% of participants) showed an LS mean treatment difference of -0.05 (p<0.05) against placebo in upper-to-lower body proportionality.
"Infigratinib is the first oral therapy designed to target FGFR3 (搜索) and directly address the underlying cause of achondroplasia (搜索)," said Dr. Savarirayan. "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."
Comprehensive Efficacy Results
PROPEL 3 was a global, one-year, 2:1 randomized, double-blinded placebo-controlled study evaluating infigratinib in children with achondroplasia (搜索) aged 3 to <18 years with open growth plates. The study achieved multiple secondary endpoints with statistical significance.
The absolute AHV at Week 52 showed significant improvement with infigratinib compared to placebo, with the treatment arm achieving 5.96 cm/year versus 4.22 cm/year on placebo - the highest LS mean absolute AHV reported to date in a randomized achondroplasia (搜索) trial.
Change from baseline in height Z-score (achondroplasia (搜索) reference population) was superior to placebo with an LS mean treatment difference of +0.32 SD (p<0.0001), representing 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 this condition.
Excellent Safety Profile
Infigratinib demonstrated a favorable safety profile throughout the study. There were no discontinuations related to study drug and no serious adverse events related to study drug. Only 3 cases (4%) of hyperphosphatemia (搜索) were reported, all characterized as mild, transient, and asymptomatic, requiring neither dose reductions nor discontinuations.
Notably, no adverse events associated with inhibition of FGFR1 (搜索) or FGFR2 (搜索) (such as retinal or corneal effects) were observed. The study also showed no adverse events associated with CNP analogues, including symptomatic hypotension, injection site reactions, or hypertrichosis.
Regulatory Pathway and Development Plans
Based on these results, BridgeBio intends to meet with regulatory authorities to discuss submission plans for a New Drug Application (NDA) and Marketing Authorization Application (MAA) for infigratinib in the second half of 2026. Infigratinib is the only therapeutic option in development for achondroplasia (搜索) to have received Breakthrough Therapy Designation from the FDA, along with Orphan Drug Designation, Fast Track Designation, and Rare Pediatric Disease Designation.
The company plans to accelerate development of infigratinib for hypochondroplasia (搜索) and is enrolling participants in the observational run-in for the Phase 3 trial. BridgeBio also continues an ongoing clinical trial of infigratinib for newborns to children under 3 years old in the PROPEL Infant & Toddler trial.
Clinical Impact and Community Response
Achondroplasia (搜索) affects 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 impacts overall health and quality of life, leading to medical complications such as obstructive sleep apnea (搜索), middle ear dysfunction, kyphosis (搜索), and spinal stenosis (搜索).
"There remains a significant unmet need for therapeutic options that are effective, practical, and less invasive for children living with achondroplasia (搜索)," 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 (搜索) overactivity to address important clinical needs, while fitting into daily life for families who are seeking a non-injectable option."
Michael Hughes, Chair of the Biotech Industry Liaison Committee at Little People of America (搜索), emphasized the significance of these results: "Today's announcement represents another milestone in achondroplasia (搜索) 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."