BridgeBio data for dwarfism drug sets up showdown with BioMarin's Voxzogo

BridgeBio Pharma reported positive Phase III results for its oral achondroplasia therapy infigratinib, setting up the experimental drug as a potential challenger to BioMarin Pharmaceutical's injectable treatment Voxzogo (vosoritide). BridgeBio shares were up about 15% in pretrade Thursday, but scaled back to roughly 8% by mid-morning.

Infigratinib is a selective inhibitor of FGFR3 designed to target the underlying cause of achondroplasia — a gain-of-function mutation in the FGFR3 gene. This specific mutation leads to overactivity of the FGFR3 protein, which slows endochondral bone growth and cartilage development, resulting in disproportionate short stature and other skeletal changes such as larger head, smaller facial features and limited elbow extension.

The PROPEL 3 study involves an estimated 110 children aged 3 to under 18 years with open growth plates who were randomised to once-daily infigratinib or placebo. The trial met its primary endpoint, with patients on infigratinib achieving a mean treatment difference in annualised height velocity (AHV) from baseline of +2.10 cm/year compared to placebo through week 52, slightly lower than earlier Phase II results.

On key secondary goals, infigratinib was also significantly better than placebo on height Z-score, when measured against an achondroplasia reference population, with a least squares (LS) mean treatment difference of +0.32 SD.

Additionally, in an exploratory analysis among children younger than 8 years, who made up more than half of trial participants, the therapy achieved the first statistically significant improvement in upper-to-lower body proportionality, showing an LS mean treatment difference of -0.05 against placebo. Across the overall population, the proportionality measure showed a difference -0.02, which wasn't statistically significant.

Ravi Savarirayan, global lead investigator for PROPEL 3, said infigratinib demonstrated the "highest and most significant improvement in annualised 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."

Safety findings showed the drug was well tolerated, with no discontinuations or serious adverse events (AEs) linked to treatment. Investigators reported three cases (4%) of hyperphosphatemia, a known effect of FGFR inhibition, all of which were "mild and transient," with none requiring dose reduction or discontinuations. The study also reported no AEs associated with FGFR1 or FGFR2 inhibition, such as retinal or corneal complications.

Marketing applications planned

BridgeBio now plans to submit regulatory filings in the US and Europe in the second half and also said it was accelerating Phase III development of infigratinib in hypochondroplasia, a less severe form of the disease.

Commenting on the PROPEL 3 readout, analyst Mani Foroohar of Leerink Partners said that "with this outcome, we believe [BridgeBio] shares could add another ~$2B in value (+15%) as infigratinib is positioned to take leading share with superior growth and proportionality." He added the therapy could unlock a "sizeable" market opportunity and potentially become the "treatment of choice, driven by best-in-class efficacy and convenience."

The global market for achondroplasia treatments is currently dominated by Voxzogo, a C-type natriuretic peptide analogue that is given as a daily subcutaneous injection. The drug was approved for achondroplasia by US and EU regulators in 2021, and BioMarin has said it is looking to expand its label to several other indications by 2031, including hypochondroplasia in 2027.

Meanwhile, another potential contender could be approved later this month. Ascendis Pharma is anticipating an FDA decision by Feb. 28 for its proposed achondroplasia treatment TransCon CNP (navepegritide). The review was delayed late last year after updated material related to post-marketing requirements were submitted.