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 effects1,2
Learn more about the multi systemic effects of 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.
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 Watch the video to learn how infigratinib may impact FGFR-driven skeletal dysplasias like achondroplasia.
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.
For more details, visit
clinicaltrials.gov
PROPEL, PROPEL 2, and PROPEL 2 OLE trial designs ENDO 2022
Infigratinib in children with achondroplasia: design of the PROPEL, PROPEL 2, 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…
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…
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
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
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 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…
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…
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…
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…
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
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
No changes in phosphorous levels
Low-dose infigratinib treatment does not lead to changes in phosphorus in preclinical animal studies
Maribel Reyes, Uma Sinha, Gary Li, David Martin
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
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
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