RARE Daily

BridgeBio Reports Durable Month 12 and 18 from Phase 2 Achondroplasia Study

June 4, 2024

Rare Daily Staff

BridgeBio Pharma reported sustained positive results from PROPEL 2, a phase 2 trial of the experimental therapy infigratinib in children with achondroplasia, demonstrating continued potential best-in-class efficacy and an encouraging 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 variant in FGFR3.

Infigratinib is an oral small molecule designed to inhibit FGFR3 signaling and target achondroplasia and hypochondroplasia at their source.

To date, key results from the Cohort 5 dose escalation cohort in PROPEL 2 trial include sustained and statistically significant mean increase in annualized height velocity (AHV) of +2.51cm/year from baseline at 12 months, and +2.50 cm/yr at 18 months; statistically significant improvement in body proportionality (mean upper to lower body segment ratio), from 2.02 at baseline to 1.88 at Month 18 (mean change from baseline); and a continued well-tolerated safety profile, with no treatment-related adverse events assessed as related to infigratinib.

“These data indicate that treatment with infigratinib is continuing to show increased growth velocity and improvements in body proportionality in children with achondroplasia. This is encouraging and suggests that infigratinib has the potential to enhance functionality for people living with achondroplasia in addition to increasing growth,” said Ravi Savarirayan of Murdoch Children’s Research Institute in Melbourne, Australia, and the global lead investigator for PROPEL 2. “We hope to see these improvements reflected in the ongoing PROPEL 3 pivotal study that will build toward providing a safe and effective oral therapy to those in the achondroplasia community who are seeking treatment.”

PROPEL 3, the global phase 3 registrational study of infigratinib in achondroplasia, continues to enroll on schedule, with completion of enrollment anticipated by the end of the year.

Given the promising results from PROPEL 2, BridgeBio is expanding the FGFR3-related skeletal dysplasias franchise for infigratinib by accelerating development in hypochondroplasia, a similar rare skeletal dysplasia, with a small open-label phase 2 portion testing a single dose of 0.25 mg/kg/day, leading into a double-blinded, placebo-controlled phase 3 study.

ACCEL, the observational lead-in program for hypochondroplasia, was initiated with the first participant consented in May 2024. The interventional program, ACCEL 2/3, will be a global phase 2/3 multicenter, single-dose study, to evaluate the efficacy and safety of 0.25mg/kg/day of infigratinib in children living with hypochondroplasia. The open-label phase 2 portion in children aged 5 to 11 years old will be followed by a pivotal phase 3, one-year, 2:1 randomized, double-blinded, placebo-controlled study in children aged 3 to less than 18 years old with growth potential. In addition to changes from baseline in AHV measurements, the study will evaluate changes in other indicators of growth, body proportions, medical complications associated with hypochondroplasia, and changes in quality-of-life measures.

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