RARE Daily

Bridgebio Reports Positive Mid-Stage Data of Infigratinib in Achondroplasia

March 6, 2023

Rare Daily Staff

BridgeBio Pharma reported positive results from a phase 2 trial of the investigational therapy infigratinib in children with achondroplasia, demonstrating potential best-in-class efficacy and a clean safety profile.

Achondroplasia is the most common cause of disproportionate short stature, affecting approximately 55,000 people in the United States and European Union, including up to 10,000 children and adolescents with open growth plates. Achondroplasia impacts overall health and quality of life, leading to medical complications such as obstructive sleep apnea, middle ear dysfunction, kyphosis, and spinal stenosis. The condition is uniformly caused by an activating mutation in FGFR3.

Infigratinib is an oral small molecule designed to inhibit FGFR3 and target achondroplasia at its source. In the highest dose cohort of the PROPEL2 trial, infigratinib increased the pace of growth in 10 children by about 3 centimeters per year from baseline, with mean increase from baseline in annualized height velocity (AHV) for the 10 children that have had six-month visits +3.03 cm/yr.

The baseline AHV for the 10 children with six-month visits was in the expected range for children with achondroplasia at 3.73 cm/yr, rising to 6.77 cm/yr after treatment. The two remaining children who have not yet had six months of follow-up have a mean change from baseline in AHV of +8.8 cm/yr at three months. The mean age for the cohort was 7.24 years. Eighty percent of the 10 children with six-month visits were responders, with a change from baseline AHV of at least 25 percent. Among the responders, the average change from baseline in AHV was +3.81 cm/yr. As a result of treatment, the median absolute AHV reached 7.6 cm/yr, which is beyond the 99th percentile of growth for children living with achondroplasia.

Preliminary analysis of collagen X (CXM) levels also saw a statistically significant increase from baseline in Cohort 5. CXM is the gold-standard biomarker of chondrocyte-driven growth and further validates the robust response to infigratinib.

Combined with the previously reported Cohort 4 change from baseline in AHV value of +1.52 cm/yr, the Cohort 5 data demonstrate a strong dose response for infigratinib. Median follow-up across all cohorts is 71.1 weeks. To date, the study has shown a well-tolerated safety profile, with no study drug related treatment emergent adverse events in Cohort 5. No serious adverse events or discontinuations due to AEs were reported in any cohort.

“These results reach a new tier of efficacy, and coupled with our differentiated safety and convenience profile, provide us the opportunity to serve children with achondroplasia and other skeletal dysplasias. We look forward to exploring the potential of infigratinib on the wider medical and functional impacts of achondroplasia, hypochondroplasia, and other skeletal dysplasias, which hold significant unmet needs for families,” said Neil Kumar, founder and CEO of BridgeBio.

Based on the positive results to date, BridgeBio has started enrolling children in the run-in for a phase 3 trial. Additionally, BridgeBio expects to initiate clinical development for infigratinib in hypochondroplasia, a skeletal dysplasia closely related to achondroplasia and similarly driven by FGFR3 gain-of-function variants. BridgeBio has previously presented promising preclinical data for hypochondroplasia at ENDO 2022 and ASHG 2022.

Photo: Neil Kumar, founder and CEO of BridgeBio

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