An oral treatment for achondroplasia, the most common form of dwarfism, is on the cusp of becoming an alternative to injections after the release of phase III trial results.

The research, led by Murdoch Children’s Research Institute (MCRI) in partnership with BridgeBio Pharma Inc. and published in the New England Journal of Medicine, found the drug infigratinib significantly improved bone growth and body proportionality in children with achondroplasia. The findings from PROPEL 3, presented at the International Conference for Children’s Bone Health in Montreal, builds on the team’s earlier phase I and phase II findings.

If approved by health regulators, infigratnib could offer families an alternative to daily injections while continuing to target the underlying cause of the condition.

MCRI Professor Ravi Savarirayan, who leads the international research team, said the results represented an important milestone in the development of new precision medicines for achondroplasia.

“This study builds on years of international research and collaboration aimed at improving health outcomes and quality of life for children with achondroplasia,” he said. “Continued scientific innovation is giving affected families more precision treatment options than ever before.”

Image: Professor Ravi Savarirayan

How does the drug target achondroplasia’s underlying cause?

Affecting about one in 20,000 babies in Australia, achondroplasia is caused by an overactive FGFR3 protein that slows the growth of bones. It can lead to serious health problems, including sudden infant death, spinal cord compression, sleep apnoea and bowed legs.

Rather than treating the complications, infigratinib is designed to selectively target FGFR3 and address the biological pathway behind the condition.

PROPEL 3, the global phase III trial, sponsored by BridgeBio Pharma Inc, involved 114 children across 10 countries, aged three to 17 years, with achondroplasia, who received either a once-daily oral infigratinib capsule or a placebo for one year. It found children who took infigratinib grew an average of 2.1cm more over the 12 months. The treatment was well tolerated, with no serious side effects linked to the medicine.

Importantly, they also became the first participants in a randomised controlled achondroplasia trial to show statistically significant improvement in body proportionality. 

Professor Savarirayan said the improvements in body proportionality were particularly encouraging.

“Improving growth is important, but seeing significant growth in body proportionality has the potential to improve mobility, physical function and independence for children with achondroplasia,” he said.

Building on a decade of research

The findings contribute to more than a decade of MCRI-led research into precision medicines for achondroplasia.

Professor Savarirayan’s team led the international clinical trials that established vosoritide as the first approved treatment in Australia for children with achondroplasia. Vosoritide, a daily injection, was added to the PBS in 2023. He also oversaw clinical trials supporting the international approval of navepegritide, a weekly injectable therapy, and is now leading global clinical development of dabogratinib, another oral option.

Professor Savarirayan said the latest findings highlighted the growing pipeline of therapies being developed for achondroplasia.

BridgeBio Pharma Inc plans to seek regulatory approval for infigratinib later this year.

He also led clinical trials supporting the international approval of navepegritide, a weekly injectable treatment, and is now leading global clinical development of dabogratinib, another more selective oral option.

Researchers from John Hopkins University, Guy’s and St. Thomas’ NHS Foundation Trust, Sheffield Children’s NHS Foundation Trust, Medical Innovation Knowledge Sharing Hospital, Centre Hospitalier Universitaire Sainte-Justine, University Hospitals Bristol and Weston NHS Foundation Trust, University of Cincinnati, Université Paris Cité, Toulouse University Hospital, Norwegian Center for Rare Diseases, UCSF Benioff Children’s Hospital Oakland, University of Missouri, Haukeland University Hospital, KK Women’s and Children’s Hospital, University of Alberta–Stollery Children’s Hospital, University of Wisconsin Hospital Universitario Virgen de la Victoria, Instituto de Investigación Biomédica de Málaga, Plataforma Bionand, Hospital Quironsalud Málaga, Universidad Europea de Andalucía, NHS Greater Glasgow and Clyde, Università Cattolica del Sacro Cuore, Vanderbilt Health, Hospital de Pediatría Garrahan, Children’s Hospital of Eastern Ontario, University of Ottawa, Hôpital Femme Mère Enfant, Hospices Civils de Lyon, Manchester University NHS Foundation Trust and University of Manchester, Children’s Hospital at London Health Sciences Centre, Children’s Hospital of Colorado and BridgeBio Pharma also contributed to the study.

Publication

Ravi Savarirayan, Julie Hoover-Fong, Melita Irving, Paul Arundel, Josep Maria de Bergua, Philippe M. Campeau, Toby Candler, Benjamin T. Cocanougher, Valerie Cormier-Daire, Thomas Edouard, Svein O. Fredwall, Paul Harmatz, Daniel Hoernschemeyer, Henrik U. Irgens, Saumya Jamuar, Peter Kannu, Janet M. Legare, Antonio Leiva-Gea, Helen McDevitt, Roberta Onesimo, John Phillips, Mariana del Pino, Marie-Eve Robinson, Massimiliano Rossi, Mars Skae, Leanne M. Ward, Klane K. White, Jane Schmidt, Ted Lystig, Ariana Salvatici, Yun Bai, Peter W. Butler, David van Veenhuyzen and Daniela Rogoff. ‘Phase 3 Trial of Oral Infigratinib in Children with Achondroplasia,’ The New England Journal of Medicine. DOI: 10.1056/NEJMoa2604565

Funding

The study was funded by Bridge Bio Pharma Inc.