FDA grants Breakthrough Therapy to oral infigratinib for children with achondroplasia

FDA grants Breakthrough Therapy to oral infigratinib for children with achondroplasia | Image Credit: © Araki Illustrations - © Araki Illustrations - stock.adobe.com.

The FDA has granted Breakthrough Therapy Designation for oral infigratinib (BridgeBio Pharma), which is currently under development for children with achondroplasia, according to a press release from BridgeBio.¹

A form of skeletal dysplasia, achondroplasia is the most common, occurring in approximately 1 in every 40,000 births according to Johns Hopkins Medicine. The skeletal dysplasia impairs the growth of the bone in the limbs and causes abnormal growth in the spine and skull. Though the cause is result of a genetic mutation, approximately 1 out of 5 cases is hereditary and passed by the parent.²

The designation from the federal agency was received based on the phase 2 PROPEL 2 (NCT04265651) clinical trial. In the prospective, open-label study of infigratinib among children aged 3 to 11 years, the primary endpoints included treatment-emergent adverse events and change from baseline in annualized height velocity.³

According to BridgeBio Pharma, infigratinib resulted in a statistically significant and sustained increase in annualized height velocity with a mean change from baseline of +2.51cm/yr at Month 12, and +2.50 cm/yr at Month 18 (P = 0.0015). Also observed was a statistically significant improvement in body proportionality at 18 months (P = 0.001).¹

“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," said Adora Ndu, PharmD, JD, chief, Regulatory Affairs officer, BridgeBio, in a statement. "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."¹

The phase 3 PROPEL 3 (NCT06164951) global registrational study of infigratinib in achondroplasia is enrolling on schedule, which is expected to be completed by the end of 2024. Infigratinib has also received Orphan Drug Designation, Fast Track Designation, and Rare Pediatric Disease Designation from the FDA.

"The reality is that achondroplasia is a skeletal dysplasia which could impact aspects of health-related quality of life and functionality," said Munira Shamim, the founder of Growing Stronger, a US advocacy group the care of individuals with achondroplasia. "This action represents a significant step towards offering the first oral treatment option more readily for families living with achondroplasia. Having a wider range of therapies empowers families with greater control and choice over their healthcare decisions."

References:

1. BridgeBio announces infigratinib is the first ever investigational therapeutic option for achondroplasia to be awarded Breakthrough Therapy Designation by the FDA. BridgeBio Pharma. Press release. September 17, 2024. Accessed September 18, 2024. https://investor.bridgebio.com/news-releases/news-release-details/bridgebio-announces-infigratinib-first-ever-investigational
2. Achondroplasia. Johns Hopkins Medicine. Accessed September 18, 2024. https://www.hopkinsmedicine.org/health/conditions-and-diseases/achondroplasia#:~:text=Achondroplasia%20is%20a%20genetic%20condition,cartilage%20of%20the%20growth%20plate
3. Savarirayan R, De Bergua JM, Arundel P, et al. Infigratinib in children with achondroplasia: the PROPEL and PROPEL 2 studies. Ther Adv Musculoskelet Dis. 2022 Mar 21;14:1759720X221084848. doi: 10.1177/1759720X221084848. PMID: 35342457; PMCID: PMC8941703