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Learn more about achondroplasia Learn more about hypochondroplasia
two children with achondroplasia smiling outdoors

About achondroplasia

Clinical manifestations

Achondroplasia is a rare, genetic, skeletal dysplasia. It has distinct clinical features including short stature with disproportionate shortening of limbs relative to trunk, macrocephaly with frontal bossing and midfacial hypoplasia with depressed nasal bridge, hypotonia, and joint hypermobililty. Achondroplasia may lead to multisystemic health effects.1,2

Learn more about the multi systemic effects of achondroplasia

FGFR3 signaling in achondroplasia

Achondroplasia is an FGFR3-driven skeletal dysplasia caused by activating pathogenic variants of the FGFR3 gene. FGFR3 downstream signaling is responsible for regulating skeletal bone growth by inhibiting chondrocyte proliferation and differentiation.3 Watch the video for more information on FGFR3 signaling and its dysregulation in achondroplasia.

FGFR3 signaling and its dysregulation in achondroplasia

What is being studied?

Infigratinib for achondroplasia

We are studying whether an investigational agent (infigratinib) has the potential to address the root cause of irregular bone growth in achondroplasia, by decreasing the overactivity of the FGFR3 receptor.4  It is the only oral agent under investigation for achondroplasia and is currently being studied in the PROPEL clinical program.4-7

Infigratinib is not currently approved for the treatment of achondroplasia by the U.S. FDA or any other health authority.

Explore our research

For more details, visit clinicaltrials.gov

Achondroplasia information

External resources

Consensus statement

International Consensus Statement on the diagnosis, multidisciplinary management and lifelong care of individuals with achondroplasia

Ravi Savarirayan , Penny Ireland, Melita Irving, Dominic Thompson, Inês Alves, Wagner A. R. Baratela, James Betts, Michael B. Bober, Silvio Boero, Jenna…

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Comprehensive clinical review

Achondroplasia: a comprehensive clinical review

Richard M. Pauli

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Preclinical mechanisms

Tyrosine kinase inhibitor NVP-BGJ398 functionally improves FGFR3-related dwarfism in mouse model

Davide Komla-Ebri, Emilie Dambroise, Ina Kramer, Catherine Benoist-Lasselin, Nabil Kaci, Cindy Le Gall, Ludovic Martin, Patricia Busca, Florent Barbault, Diana Graus-Porta, Arnold Munnich, Michaela Kneissel, Federico Di Rocco, Martin Biosse-Duplan, and Laurence Legeai-Mallet

View article

Achondroplasia references

About hypochondroplasia

Clinical manifestations

Hypochondroplasia is a skeletal dysplasia characterized by disproportionate short stature.1 Common additional musculoskeletal manifestations include genu varum, limited elbow extension, lumbar lordosis, generalized joint laxity, and spinal stenosis.1 Respiratory complications, such as recurrent otitis media and sleep apnea, as well as epilepsy and neurocognitive difficulties, are also associated with the condition.2,3 Due to the considerable variability in clinical presentation, diagnosis of hypochondroplasia can be challenging.1,4

smiling toddler playing outdoors

Diagnosis1,4

Hypochondroplasia may be detected and diagnosed prenatally by sonography with subsequent molecular confirmation. More typically, a diagnosis is made after birth through clinical evaluation, radiological assessment, and genetic testing.

medical professionals discussing hypochondroplasia at a meeting with a laptop

FGFR3 signaling in skeletal dysplasias

FGFR3-driven skeletal dysplasias are caused by activating pathogenic variants of the FGFR3 gene. FGFR3 downstream signaling is responsible for regulating skeletal bone growth by inhibiting chondrocyte proliferation and differentiation.3 Watch the video for more information on FGFR3 signaling and its dysregulation in achondroplasia.

FGFR3 signaling and its dysregulation in hypochondroplasia

What is being studied?

Infigratinib for hypochondroplasia

The ACCEL clinical program is designed to deepen our understanding of the natural history of hypochondroplasia and the medical outcomes that may be impacted by FGFR3 inhibition.

Infigratinib, an oral investigational agent, may impact FGFR3-driven skeletal dysplasias, such as hypochondroplasia.

Infigratinib is not currently approved for the treatment of hypochondroplasia by the U.S. FDA or any other health authority.

Hypochondroplasia references

The complete details of the study design are available

Learn more

Resources

Latest data releases

poster of activity in murine models of achondroplasia and hypochondroplasia

Activity in murine models of achondroplasia and hypochondroplasia

Elena Muslimova, Benoit Demuynck, Léa Loisay, Morgan Paull, Laurence Legeai-Mallet

poster of bone mineral density in a cohort of children with ach participating in the propel studies

Bone mineral density in a cohort of children with ACH participating in the PROPEL studies

Ravi Savarirayan, Josep Maria De Bergua, Paul Arundel, Jean Pierre Salles, Antonio Leiva-Gea, Melita Irving, Vrinda Saraff, Helen McDevitt, Maria Salcedo Montejo, Marc Nicolino, Valerie Cormier-Daire, Peter Kannu, Mars Skae, Michael B. Bober, John Phillips III, Toby Candler, Paul Harmatz, Howard Saal, Julie Hoover-Fong, Elena Muslimova, Terry Cho, Richard Weng, Daniela Rogoff

poster of infigratinib in children with achondroplasia design of the propel, propel2, and propel ole studies

Infigratinib in children with achondroplasia: Design of the PROPEL, PROPEL2, and PROPEL OLE studies

Ravi Savarirayan, Josep Maria De Berga, Paul Arundel, Helen McDevitt, Valerie Cormier-Daire, Vrinda Saraff, Mars Skae, Borja Delgado, Antonio Leiva-Gea, Fernando Santos-Simarro, Jean Pierre Salles, Marc Nicolino, Massimiliano Rossi, Peter Kannu, Michael B. Bober, John Phillips III, Howard Saal, Paul Harmatz, Christine Burren, Garrett Gotway, Terry Cho, Elena Muslimova, Richard Weng, Daniela Rogoff, Julie Hoover-Fong, Melita Irving

PROPEL and PROPEL2 trials in progress

poster of propel, propel2, and propel ole trial designs endo 2022

PROPEL, PROPEL2, and PROPEL2 OLE trial designs ENDO 2022

Infigratinib in children with achondroplasia: design of the PROPEL, PROPEL2, and PROPEL OLE studies

Ravi Savarirayan, Josep Maria De Berga, Paul Arundel, Helen McDevitt, Valerie Cormier-Daire, Vrinda Saraff, Mars Skae, Borja Delgado, Antonio Leiva-Gea…

poster of propel, propel2, and propel ole trial designs endo 2022

PROPEL trial design and baseline characteristics data ASBMR 2021

Study design and baseline characteristics of children enrolled in PROPEL: a prospective clinical assessment study in children with achondroplasia

Ravi Savarirayan, Josep Maria De Berga, Paul Arundel, Jean Pierre Salles, Antonio Leiva-Gea, Vrinda Saraff, Helen McDevitt, Fernando Santos-Simarro…

poster of propel2 trial design asbmr 2021

PROPEL2 trial design ASBMR 2021

PROPEL2: a phase 2, open-label, dose-escalation and dose-expansion study of infigratinib in children with achondroplasia

Ravi Savarirayan, Paul Arundel, Josep Maria De Bergua, Helen McDevitt, Valerie Cormier-Daire, Vrinda Saraff, Mars Skae, Fernando Santos-Simarro, Jean Pierre

poster of propel2 trial design endo 2021

PROPEL2 trial design ENDO 2021

Infigratinib in children with achondroplasia (ACH): design of PROPEL2 – a phase 2, open-label, dose-escalation and dose-expansion study

Ravi Savarirayan, Peter Kannu, Carl L. Dambkowski, Daniela Rogoff, Melita Irving

poster of propel bmi and metabolism

PROPEL trial design ENDO 2020

Prospective clinical assessment study in children with achondroplasia: the PROPEL trial

Ravi Savarirayan, Peter Kannu, Carl L. Dambkowski, Daniela Rogoff, Melita Irving

PROPEL natural history data

poster of propel medical history

PROPEL BMI and metabolism

Evaluation of body mass index and metabolic parameters in children with achondroplasia participating in the PROPEL study

Ravi Savarirayan, Josep Maria De Bergua, Paul Arundel, Jean Pierre Salles, Antonio Leiva-Gea, Melita Irving, Vrinda Saraff, Helen McDevitt, Fernando…

poster of propel medical history

PROPEL medical history

Medical history of children enrolled in PROPEL: a prospective clinical assessment study in children with achondroplasia

Ravi Savarirayan, Josep Maria De Bergua, Paul Arundel, Jean Pierre Salles, Antonio Leiva-Gea, Vrinda Saraff, Helen McDevitt, Fernando Santos-Simarro…

Quality of life research

poster of medical challenges and impacts

Medical challenges and impacts

Qualitative research in children with achondroplasia and parents of children with achondroplasia: medical challenges and impacts

Susan D. Mathias, Julie Hoover-Fong, Ravi Savarirayan, Chandler Crews, Inês Alves, Susana Noval Iruretagoyena, Amer Haider, Terry Cho, Anne Lee, Hilary…

poster of qualitative research on patient-reported outcome measures

Qualitative research on patient-reported outcome measures

Qualitative research in children and parents of children with achondroplasia to cognitively debrief three patient-reported outcome measures and confirm the content validity of a clinically assessed measure

Susan D. Mathias, Julie Hoover-Fong, Ravi Savarirayan, Chandler Crews, Inês Alves, Susana Noval Iruretagoyena, Amer Haider, Terry Cho, Anne Lee, Hilary…

Infigratinib preclinical research

poster of activity in preclinical models of hypochondroplasia

Activity in preclinical models of hypochondroplasia

Low-dose infigratinib, an oral selective fibroblast growth factor receptor tyrosine kinase inhibitor, demonstrates activity in preclinical models of hypochondroplasia

Carl Dambkowski, Benoit Demuynck, Léa Loisay, Laurence Legeai-Mallet

poster of potency and selectivity of fgfr-selective tkis

Potency and selectivity of FGFR-selective TKIs

FGFR-selective tyrosine kinase inhibitors, such as infigratinib, show potency and selectivity for FGFR3 at pharmacologically relevant doses for the potential treatment of achondroplasia

Katherine Dobscha, Ge Wei, Carl L Dambkowski, Daniela Rogoff

poster of therapeutic approach in a preclinical achondroplasia model

Therapeutic approach in a preclinical achondroplasia model

Support for a new therapeutic approach of using a low-dose FGFR tyrosine kinase inhibitor (infigratinib) for achondroplasia

Benoit Demuynck, Justine Filpo, Gary Li, Carl Dambkowski, Laurence Legeai-Mallet

poster of activity in a preclinical achondroplasia model

Activity in a preclinical achondroplasia model

Low dose, daily or intermittent administration of infigratinib (BGJ398), a selective FGFR inhibitor, as treatment for achondroplasia in a preclinical mouse model

Benoit Demuynck, Gary Li, Carl Dambkowski, Laurence Legeai-Mallet