ESPE Abstracts (2024) 98 FC15.4

ESPE2024 Free Communications Late Breaking (6 abstracts)

Oral infigratinib for children with achondroplasia: Month 18 results from the PROPEL 2 study demonstrate safety and durability of treatment effect on linear growth with improved body proportionality

Ravi Savarirayan 1 , Josep Maria De Bergua 2 , Paul Arundel 3 , Jean Pierre Salles 4 , Vrinda Saraff 5 , Borja Delgado 6 , Antonio Leiva-Gea 6 , Helen McDevitt 7 , Marc Nicolino 8 , Massimiliano Rossi 8 , Maria Salcedo 9 , Valerie Cormier-Daire 10 , Mars Skae 11 , Peter Kannu 12 , John Phillips III 13 , Howard Saal 14 , Paul Harmatz 15 , Toby Candler 16 , Elena Muslimova 17 , Richard Weng 17 , Yun Bai 17 , Supriya Raj 1 , Julie Hoover-Fong 18 , Melita Irving 19 & Daniela Rogoff 17


1Murdoch Children’s Research Institute, Melbourne, Australia. 2Hospital Vithas San José, Vitoria-Gasteiz, Spain. 3Sheffield Children’s NHS Foundation Trust, Sheffield, United Kingdom. 4Hôpital des Enfants – Toulouse, Toulouse, France. 5Birmingham Women’s and Children’s NHS Foundation Trust, Birmingham, United Kingdom. 6Hospital Universitario Virgen de la Victoria, Malaga, Spain. 7NHS Greater Glasgow and Clyde, Glasgow, United Kingdom. 8Hôpital Femme Mère Enfant, Hospices Civils de Lyon, Lyon, France. 9Hospital Universitario La Paz, Madrid, Spain. 10Hôpital Necker-Enfants Malades, Paris, France. 11Manchester University NHS Foundation Trust, Manchester, United Kingdom. 12University of Alberta – Stollery Children’s Hospital, Edmonton, Canada. 13Vanderbilt University Medical Center, Nashville, USA. 14Cincinnati Children’s Hospital Medical Center, Cincinnati, USA. 15Benioff Children’s Hospital Oakland, Oakland, USA. 16University Hospitals Bristol and Weston NHS Foundation Trust, Bristol, United Kingdom. 17QED Therapeutics, a BridgeBio company, San Francisco, USA. 18Johns Hopkins University, Baltimore, USA. 19Guy’s and St Thomas’ NHS Foundation Trust, London, United Kingdom


Objectives: Achondroplasia (ACH) is characterized by disproportionate short stature and is associated with medical complications and functional constraints. Infigratinib is an oral FGFR3 inhibitor that targets overactive FGFR3 signaling at its origin and is under development as a treatment option for children with ACH. We report Month 18 results from PROPEL 2 (NCT04265651), a Phase 2, multicenter, open-label, dose-escalation and dose-expansion study to evaluate the preliminary safety, tolerability, and efficacy of infigratinib in children with ACH aged 3-11 years at screening.

Methods: All subjects completed ≥6 months of growth assessments in the observational PROPEL study (NCT04035811) prior to enrollment in PROPEL 2. The 6-month dose-escalation phase of PROPEL 2 comprised 5 ascending dose cohorts ranging from 0.016 mg/kg/day to 0.25 mg/kg/day, followed by a 12-month extended treatment period. Annualized height velocity (AHV), height z-score and body proportion ratio were analyzed for up to 18 months. Safety is presented across cohorts. Efficacy results are presented for Cohort 5.

Results: 72 children enrolled (58.3% female; mean (SD) age = 7.5 (2.2) years; age range 3.1 – 11.5 years) and 67 completed 18 months of treatment. All children experienced at least one TEAE, with the most common ones in the category of infections and infestations. No SAEs or TEAEs led to treatment discontinuation. A statistically significant increase in AHV was observed in children in Cohort 5 (0.25 mg/kg/day), with a mean (SD) change from baseline in AHV at Month 6 of +3.38 (2.70) cm/year (P = 0.0012, n = 12), which persisted at Month 12 (+2.51 (2.21) cm/year, P = 0.0037, n = 11) and Month 18 (+2.50 (1.91) cm/year, P = 0.0015, n = 11). Of 10/11 children with positive AHV changes from baseline at Month 18, 73% experienced a >25% AHV increase. Mean (SD) change from baseline in height z-score was +0.54 (0.28) (P <0.0001) at Month 18 relative to an untreated ACH population. A statistically significant improvement in upper:lower body segment ratio was observed, with mean (SD) change from baseline of -0.12 (0.09) (P = 0.0012) at Month 18.

Conclusions: Oral infigratinib was well-tolerated for up to 18 months. Daily doses of 0.25 mg/kg infigratinib resulted in significant and sustained increases in AHV as well as improvement in body proportionality, suggesting the potential to provide meaningful benefits to children with ACH. The safety and efficacy of oral infigratinib at the 0.25 mg/kg/day dose are currently being evaluated in PROPEL 3, a phase 3, randomized, placebo-controlled study (NCT06164951).

Volume 98

62nd Annual ESPE (ESPE 2024)

Liverpool, UK
16 Nov 2024 - 18 Nov 2024

European Society for Paediatric Endocrinology 

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