BridgeBio gains on phase 3 dwarfism data

Shares in BridgeBio were ticking up today after it revealed data from its phase 3 trial of infigratinib in achondroplasia, the most common form of dwarfism, that could form the basis of regulatory filings.

A daily oral dose of the FGFR3 inhibitor was shown to improve annualised height velocity (AHV) compared to placebo by around 2cm per year in the PROPEL 3 study, which involved children younger than eight with achondroplasia, and also improved body proportionality in a subgroup of three- to eight-year-olds.

The drug was also well tolerated, with three cases of mild elevations in phosphate levels and no serious toxicities or dropouts due to side effects.

BridgeBio said it plans to file for approval of infigratinib in the US and Europe in the second half of this year, and – if approved – it could provide an oral alternative to BioMarin's Voxzogo (vosoritide), an FGFR3 analogue that has been on the market as a treatment for achondroplasia since 2021 and is administered as a daily, weight-adjusted subcutaneous injection.

Voxzogo, which is currently the only approved therapy for achondroplasia in the US and Europe and is available in more than 50 countries worldwide, was approved on the basis of a 1.4cm to 1.5cm improvement in AHV compared to placebo in its pivotal phase 3 trial.

BioMarin has forecast that sales for full-year 2025 could be more than $900 million, putting the product on course to clear the billion-dollar blockbuster threshold in 2026.

"Achondroplasia is a genetic condition driven by FGFR3 that affects more than stature alone, with consequences on physical functioning and independence that can impact widely over a person's lifetime," said PROPEL 3 lead investigator Ravi Savarirayan of Murdoch Children's Research Institute in Melbourne, Australia.

"These best-in-class results highlight the transformative potential for infigratinib to address aspects of achondroplasia beyond linear height, and with a product administered orally," he added.

Analysts described the data for infigratinib, which has a breakthrough designation from the FDA, as a best-case scenario that bodes well for regulatory reviews of the drug and its commercial potential if approved.

Around 55,000 people are living with achondroplasia in the US and Europe, according to BridgeBio, of whom 10,000 are children and adolescents who may respond to treatment with the oral drug.

Michael Hughes, chair of the biotech industry liaison committee at the Little People of America advocacy organisation, said the improvement in body proportionality seen with one year of treatment with infigratinib "is an outcome that individuals and families have identified as meaningful [and] may be relevant to physical function."

In parallel with the filing in achondroplasia – which accounts for around 70% of all cases of dwarfism associated with disproportionate stature – BridgeBio said it is also accelerating plans to test the drug in hypochondroplasia, another, generally milder form of FGFR3-mediated dwarfism.

Hypochondroplasia tends to cause more subtle symptoms, with small effects on limbs, and by some estimates is as common as achondroplasia but underdiagnosed.

BioMarin, meanwhile, is also developing the drug in a phase 3 programme for hypochondroplasia, and has earlier-stage studies ongoing in idiopathic short stature, Noonan syndrome, Turner syndrome, and SHOX deficiency.