Oral achondroplasia therapy receives FDA breakthrough therapy designation
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Key takeaways:
- Infigratinib increased annualized height velocity for children with achondroplasia in a phase 2 trial.
- BridgeBio Pharma is currently enrolling children with achondroplasia for a phase 3 trial.
An oral medication to treat children with achondroplasia has received breakthrough therapy designation from the FDA, BridgeBio Pharma announced.
The FDA has granted breakthrough therapy designation to infigratinib (BridgeBio Pharma) as a therapeutic option to treat achondroplasia. The designation was granted based on data from the PROPEL 2 phase 2 study. In the trial, children receiving infigratinib had a significant increase in annualized height velocity of 2.51 cm per year at 12 months that was sustained at 18 months at 2.5 cm per year (P = .0015). Body proportionality also improved from baseline to 18 months with infigratinib (P = .001).
The breakthrough therapy designation is the latest FDA designation granted to infigratinib. The medication previously receiving an orphan drug designation, fast track designation and rare pediatric disease designation from the FDA for the treatment of achondroplasia. According to BridgeBio Pharma, the medication would be the first-in-class oral therapy to treat children with achondroplasia if it is approved by the FDA.
“The receipt of breakthrough therapy designation, the first ever for a treatment being developed for children with achondroplasia, marks another important milestone for our skeletal dysplasia program,” Adora Ndu, PharmD, JD, chief regulatory affairs officer at BridgeBio Pharma, said in the press release. “This recognition by the FDA further confirms the strength of our phase 2 data, and the substantial improvement on clinically significant endpoints over available therapies. We are excited by what this means for the community, and we look forward to working closely with FDA to expedite the development of infigratinib and access for families to an oral option.”
BridgeBio Pharma announced it is currently enrolling participants for a phase 3 study to assess infigratinib in achondroplasia. The company announced it plans to explore the use of the drug on a range of medical and functional impacts of achondroplasia, hypochondroplasia and other skeletal dysplasias.
Perspective
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Infigratinib, a tyrosine kinase inhibitor that causes selective inhibition of the fibroblast growth factor receptors (FGFR) 1-3, has the potential to reduce hyperactivation of FGFR-3 that causes disproportionate short stature in achondroplasia. The safety profile and promising treatment response of infigratinib have led to its breakthrough therapy designation by the FDA.
Infigratinib joins the field of potential achondroplasia therapies with the transiently pegylated C-natriuretic peptide (CNP), navepegritide (TransCon CNP, Ascendis Pharma), in phase 3 clinical trials against the FDA-approved CNP analog, vosoritide (Voxzogo, BioMarin Pharmaceutical). Infigratinib is the only orally available option, and the only therapeutic that targets the achondroplasia-specific defect rather than the downstream signaling pathway. Phase 2 data in children with achondroplasia have shown sustained improved height velocity over 18 months with infigratinib therapy that is numerically superior to that seen with vosoritide or navepegritide. In addition, there are data supporting an improvement in proportions.
Although improved height is a measurable clinical trial endpoint, it is not the ultimate goal of therapies for achondroplasia. The goal of therapy is reduced long-term skeletal and neurologic complications. The early data for infigratinib and the other therapies show promise for reaching this goal, but long-term follow-up will be necessary to document these potential benefits.
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