BridgeBio Pharma (NASDAQ:BBIO) hosted an investor webinar to outline its clinical and commercial strategy for infigratinib, an oral FGFR inhibitor being developed for achondroplasia, ahead of an expected Phase 3 top-line readout by the end of the first quarter. Management said the company recently achieved “last participant last visit” in PROPEL 3, its pivotal trial in children with achondroplasia.
Achondroplasia overview and unmet needs
Dr. Janet Lagarde, a professor in genetics and pediatrics at the University of Wisconsin School of Medicine and Public Health and an investigator in PROPEL 3, described achondroplasia as the most common form of disproportionate short stature. She said it occurs in roughly one in 25,000 people, translating to about 15,000 individuals affected in North America. While a person with achondroplasia has a 50% chance of passing the condition to a child, Lagarde noted that most people with achondroplasia are born to average-stature parents.
Infigratinib mechanism and formulation
BridgeBio Chief Medical Officer for Skeletal Dysplasia Dr. Daniela Rogoff said infigratinib is an oral “first-in-class” FGFR1/2/3 tyrosine kinase inhibitor being developed for achondroplasia. She described FGFR3 as a negative regulator of growth plate activity and said achondroplasia is driven by a gain-of-function FGFR3 variant that keeps signaling active.
Rogoff said infigratinib inhibits FGFR3 kinase activity, decreasing downstream signaling pathways. She contrasted this approach with therapies that target only a single downstream pathway. Rogoff added that, at the doses used in achondroplasia, BridgeBio expects modulation of the overactivated receptor without meaningfully inhibiting FGFR1 or FGFR2, citing Phase 2 safety data as supportive.
The company is studying infigratinib as a “sprinkle capsule” that can be swallowed whole or opened and sprinkled on soft food, with dosing based on weight.
Clinical program and Phase 2 findings
Rogoff outlined a development program comprising five studies that together are expected to evaluate infigratinib in approximately 300 children ages 0 to 18. The program includes:
- PROPEL observational study collecting baseline growth and complication data
- PROPEL 2 Phase 2 dose-finding and proof-of-concept trial in children ages 3 to 11
- PROPEL 3 Phase 3 pivotal trial
- PROPEL OLE long-term open-label extension through completion of growth
- PROPEL INT infant/toddler study in children ages 0 to 3, which the company said is underway
In PROPEL 2, the company selected a cohort 5 dose of 0.25 mg/kg/day for Phase 3 based on a balance of effect and safety. Rogoff said cohort 5 was well tolerated, with no adverse events leading to discontinuation. She also reported no observed hyperphosphatemia and no corneal or retinal adverse events in that cohort.
On efficacy, Rogoff said cohort 5 showed a sustained increase in annualized height velocity through 18 months, with a change from baseline of 2.5 cm/year at months 12 and 18. She cited a p-value of 0.0015 at month 18. She also said the height C-score increased by more than half a standard deviation at month 18 and that body proportions (upper-to-lower segment ratio) improved, reaching statistical significance at month 18 (p=0.001).
PROPEL 3 design and readout expectations
Rogoff said PROPEL 3 is a double-blind, placebo-controlled study in children ages 3 to 18 with remaining growth potential. Participants completed at least six months in the PROPEL observational study before enrolling and were randomized 2:1 to infigratinib or placebo for 52 weeks, with an option to enter the open-label extension afterward.
The primary endpoint is change from baseline in annualized height velocity versus placebo. Key secondary endpoints include change from baseline in height Z-score and in body proportions versus placebo, along with additional assessments including safety, quality of life, and participant/caregiver qualitative interviews. The company reiterated expectations for top-line results later in the first quarter.
Commercial positioning, market research, and key topics from Q&A
Justin To said BridgeBio believes infigratinib could be a market-leading option if approved, citing its oral route of administration and its targeting of FGFR3 biology. He said the company has received FDA breakthrough therapy designation in achondroplasia.
To also summarized physician survey work the company conducted with nearly 100 healthcare professionals, which he said collectively see about 40% of U.S. children with achondroplasia. He said respondents prioritized oral administration and targeting FGFR3 as leading reasons to switch therapies, ahead of incremental efficacy gains. The company also cited global prevalence estimates, stating there are over 55,000 individuals with achondroplasia and open growth plates worldwide, and described this as implying a market opportunity of over $5 billion. To added that only about 10% of eligible individuals are on a treatment today, attributing a major share of the gap to injection burden.
During Q&A, hyperphosphatemia was a key topic. To said clinicians the company spoke with were not concerned about low-grade hyperphosphatemia, particularly if below 10%, and compared that to higher rates he said are seen with daily and weekly growth hormone. Lagarde added that mild elevations are common in childhood and said she was not concerned about chronic low-grade hyperphosphatemia, emphasizing the need to interpret levels in the context of age and pubertal timing. On trial operations, To said the company does not have access to blinded safety data and noted data cleaning is ongoing ahead of database lock.
Lagarde said approximately 40% of her eligible patients are not on treatment, with injections cited as the primary reason. She added that families frequently ask about an oral option and said many patients currently on injections are “buying their time” until an oral therapy is available. On what would drive switching, Lagarde said matching the efficacy of current daily injections could be enough to prompt broad switching, and she referenced an “extra 1.57 cm per year” as a benchmark for comparable efficacy in her view.
Asked about combination approaches, Lagarde discussed weekly human growth hormone plus a CNP analog combination data set from Ascendis’ CHOICE trial, stating growth hormone responses can be strong early but may diminish over time and questioning its long-term role. She said combination therapy involving an FGFR3 inhibitor and a CNP analog could be of interest in infants, particularly to potentially reduce foramen magnum stenosis, while also raising reimbursement considerations. To said BridgeBio was not surprised by the reported combination data and argued it resembled historical growth hormone patterns.
On Phase 3 strategy, To said PROPEL 3’s broad age range (3 to 18) was intended to support the “broadest possible label,” acknowledging that other trials have shown less treatment effect at the youngest and oldest ages. He also said a separate infant/toddler study is ongoing and that the same oral formulation may be used for most children, with an alternative potentially needed for those younger than six months.
To added that BridgeBio is interested in commercialization outside the U.S., describing achondroplasia care as concentrated in centers of excellence in various countries. He also discussed competing FGFR3 inhibitor approaches, arguing that infigratinib’s current dosing is below levels expected to meaningfully inhibit FGFR1/2 and raising concerns about off-target trade-offs he said could occur with some FGFR3-selective strategies.
About BridgeBio Pharma (NASDAQ:BBIO)
BridgeBio Pharma, Inc is a clinical-stage biopharmaceutical company headquartered in Palo Alto, California. Founded in 2015 by Neil Kumar, the company is dedicated to discovering, developing and delivering transformative medicines for patients with genetic diseases and cancers. BridgeBio operates an integrated model that spans target identification, preclinical research, clinical development and commercialization, aiming to streamline the process from bench to bedside.
BridgeBio’s pipeline comprises multiple therapeutic modalities, including small molecules, biologics and genetic therapies.
