BridgeBio is hoping infigratinib will get another shot at approval after the medicine hit the key goals of a phase 3 study in a form of dwarfism in children.
The FDA granted infigratinib, which was then marketed as Truseltiq, accelerated approval in 2021 for previously treated, locally advanced or metastatic bile duct cancer with an FGFR2 fusion or rearrangement. But the regulator revoked that approval three years later on the request of BridgeBio’s then-partner Helsinn over difficulties recruiting patients for a required confirmatory trial.
But BridgeBio hasn’t lost faith in infigratinib. The company has been evaluating the FGFR1-3 selective tyrosine kinase inhibitor therapy in a global phase 3 study of children living with achondroplasia, the most common cause of dwarfism. The condition is caused by an activating variant in FGFR3.
The year-long Propel 3 study hit its primary endpoint of demonstrating a “statistically significant” mean 2.1 cm/year improvement in annualized height velocity (AHV) from baseline over placebo, according to a Feb. 12 release. When it came to the secondary endpoint of absolute height growth over the year, infigratinib showed a least squares (LS) mean improvement of 5.96 cm/year compared to 4.22 cm/year for the placebo group.
The company also drilled down into the change from baseline in upper-to-lower body proportionality among a subgroup of children under the age of 8. For these patients, infigratinib was the “first therapeutic option to show statistical significance against placebo in a randomized trial for achondroplasia,” according to BridgeBio, which pointed to a LS mean decrease of 0.05 against placebo.
There were no serious adverse events related to infigratinib, with the three cases of hyperphosphatemia—an electrolyte disorder—all classed as mild and asymptomatic.
The latest infigratinib trial follows a phase 2 study that showed mean increases in height growth of 2.51 cm/year over 12 months. The FDA approved (PDF) BioMarin’s achondroplasia therapy Voxzogo on the basis of a trial that reported a 1.40-cm/year increase in AHV at 12 months.
BridgeBio is going to take the phase 3 data to regulators in the second half of the year in a bid to get infigratinib approved for achondroplasia. Alongside this approval push, the company is also enrolling patients in a separate phase 3 study for hypochondroplasia, a milder form of achondroplasia.
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“There remains a significant unmet need for therapeutic options that are effective, practical, and less invasive for children living with achondroplasia,” BridgeBio Chief Medical Officer Daniela Rogoff, M.D., said in today’s release.
“The Propel 3 data support the potential of an oral medicine directly targeting FGFR3 overactivity to address important clinical needs, while fitting into daily life for families who are seeking a non-injectable option,” Rogoff continued. “These results represent meaningful progress for those who have been waiting for a better approach, and we look forward to advancing this program towards global submissions.”
Ravi Savarirayan, M.D., Ph.D., the global lead investigator for the Propel 3 study, described infigratinib as “the first oral therapy designed to target FGFR3 and directly address the underlying cause of achondroplasia.”
“In the broadest age range studied to date, oral infigratinib has demonstrated the highest and most significant improvement in annualized 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,” Savarirayan added.
BridgeBio isn’t the only company that has looked to challenge BioMarin for the achondroplasia market. Ascendis Pharma is finally expecting a delayed decision from the FDA to come down later this month for its dwarfism drug TransCon CNP, while Sanofi scrapped its own candidate back in 2024.
