SFEBES2026 Oral Communications Bone and Reproductive Endocrinology (6 abstracts)
Improvements in Lower Extremity Alignment are Associated with Physical Functioning in Children with Achondroplasia Treated with Navepegritide: 52-Week Results from the ApproaCH Trial
Melita Irving 1 , Leanne Ward 2 , Daniel Hoernschemeyer 3 , Janet Legare 4 , Hanne Hove 5 , Carlos Bacino 6 , Philippe Campeau 7 , Paul Hofman 8 , Josep Maria de Bergua Domingo 9 , M.Jennifer Abuzzahab 10 , Kevin Smit 11,12 , Sasha Carsen 12,13 , Andrew Tice 12,13 , Stefan Jackowski 14 , Maya Scharke 14 , Meng Mao 15 , Lærke Clement Freiberg 16 , Michael Makara 15 , Michael Ominsky 15 , Aimee Shu 15 , Ravi Savarirayan 17,18,19 & Ciara McDonnell 20,21
1Department of Clinical Genetics, Guy’s and St Thomas’ NHS Foundation Trust, London, United Kingdom; 2Children’s Hospital of Eastern Ontario, University of Ottawa, Ottawa, Canada; 3University of Missouri Children’s Hospital, Columbia, USA; 4University of Wisconsin School of Medicine and Public Health, Wisconsin, USA; 5Copenhagen University Hospital, Copenhagen, Denmark; 6Baylor College of Medicine, Texas, USA; 7CHU Sainte-Justine Research Center, Montreal, Canada; 8The Liggins Institute, University of Auckland, Auckland, New Zealand; 9Unidad de Cirugía Artroscópica, Vithas Vitoria Hospital, Vitoria- Gasteiz, Spain; 10Children’s Minnesota, Minneapolis, USA; 11Department of Surgery, Division of Pediatric Orthopedics, Children’s Hospital of Eastern Ontario, Ottawa, Canada; 12University of Ottawa, Ottawa, Canada; 13Children’s Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, Canada; 14The Ottawa Pediatric Bone Health Research Group, Children’s Hospital of Eastern Ontario Research Institute, Ottawa, Canada; 15Ascendis Pharma Inc., Palo Alto, USA; 16Ascendis Pharma A/S, Hellerup, Denmark; 17Murdoch Children’s Research Institute, Parkville, Australia; 18Royal Children’s Hospital, Parkville, Australia; 19University of Melbourne, Parkville, Australia; 20Children’s Health Ireland at Temple Street, Dublin, Ireland; 21University of Dublin, Trinity College, Dublin, Ireland
Genu varum is common in children with achondroplasia, and can lead to pain, impaired mobility, and a negative impact on health-related quality of life. In this post-hoc analysis from the pivotal ApproaCH trial we report the effects of navepegritide, a prodrug of C-type natriuretic peptide (CNP), on genu varum and its association with Achondroplasia Child Experience Measure-Physical Functioning (ACEM-PF), an achondroplasia-specific clinical outcome assessment. ApproaCH randomized 84 children (aged 2-11 years) 2:1 to receive once-weekly navepegritide (100 µg/kg/week) or placebo. Radiographs were collected at baseline and Week 52, with key features of skeletal dysplasia assessed by blinded central readers. Data are reported as least square (LS) mean differences versus placebo calculated by ANCOVA, and Pearson correlation coefficients (r). The primary endpoint—annualized growth velocity at Week 52—was greater in navepegritide-treated children versus placebo (LS mean difference 1.49 cm/year, P < 0.0001). Compared with placebo at Week 52, navepegritide significantly reduced tibial-femoral angle (TFA) (difference -1.81 degrees, P = 0.0094), significantly improved fibula-to-tibia ratio (difference -0.016, P = 0.0001), and improved ACEM-PF scores (difference -4.6, P = 0.252). Compared with the overall population, children with prominent genu varum at baseline (TFA ≥5 degrees) treated with navepegritide had greater improvements versus placebo in TFA (difference -3.99 degrees, P = 0.0073) and ACEM-PF (difference -8.2, P = 0.048). Changes in ACEM-PF were associated with improvements in TFA in children with more severe genu varum at baseline (r = 0.31; P = 0.062); the correlation was stronger in this subgroup aged <8 years (r = 0.39; P = 0.035). Navepegritide demonstrated superiority over placebo in AGV, and reduced TFA at Week 52 in the ApproaCH trial. Associations between improvements in genu varum and ACEM-PF support that changes in lower extremity alignment with once-weekly navepegritide positively impact physical functioning, and suggest that navepegritide may offer benefits beyond promoting linear growth that translate into meaningful improvements in children living with achondroplasia.
Volume 117
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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