OR36-05 Safety and Tolerability of Navepegritide Treatment in Children With Achondroplasia: 52-Week Results From the Pivotal ApproaCH Trial
Notice bibliographique
Résumé
Abstract Disclosure: C. McDonnell: Ascendis Pharma, BioMarin, Pfizer, Inc. H. Hove: Ascendis Pharma, Pfizer, Inc.. J.M. Legare: None. P.M. Campeau: Ascendis Pharma, BioMarin, Ipsen, Pfizer, Inc., Takeda. P.L. Hofman: Eli Lilly & Company, Novo Nordisk. D.G. Hoernschemeyer: BioMarin, Orthopediatrics, Zimvie. J.M. de Bergua Domingo: None. M.J. Abuzzahab: Ascendis Pharma, Endo, Inhale, Lumos, Medtronic, Novo Nordisk, Pfizer, Inc., Rhythm, Soleno. M. Mao: Ascendis Pharma. I. Ballance: Ascendis Pharma. L.C. Freiberg: Ascendis Pharma. L.W. Dalby: Ascendis Pharma. A.D. Shu: Ascendis Pharma. C.A. Bacino: Ascendis Pharma, BioMarin, Ionis Pharmaceuticals Inc., Roche. R. Savarirayan: Ascendis Pharma, BioMarin, BridgeBio. Background: Safety and tolerability are key considerations in assessing the value of emerging therapies that aim to address clinical manifestations and potentially life-threatening complications of achondroplasia (ACH). Navepegritide is an investigational prodrug of C-type natriuretic peptide (CNP), administered SC once weekly and designed to provide a low Cmax through sustained release of active CNP. Continuous exposure to the released CNP stimulates natriuretic peptide receptor B (NPR-B) to counteract the constitutively active fibroblast growth factor receptor 3 (FGFR3) characteristic of ACH. We report safety and tolerability data from ApproaCH, a pivotal, randomized, double-blind, placebo-controlled trial in which children with ACH were treated with navepegritide or placebo for 52 weeks. Based on the reported experience with an available daily CNP analogue, symptomatic hypotension and injection site reactions (ISRs) were defined as adverse events of special interest in the ApproaCH trial. Methods: Participants (N=84, aged 2-11 years) were stratified by age and sex and randomized 2:1 to receive navepegritide (100 μg/kg/week) or placebo. The primary endpoint was annualized growth velocity (AGV) at week 52. Safety and tolerability were assessed via treatment-emergent adverse events (TEAEs), laboratory values, vital signs, physical and skeletal examination, electrocardiogram, Tanner staging, bone age, and bone-related safety events. Results: Navepegritide demonstrated AGV superiority over placebo with an LS mean AGV of 5.89 cm/year vs. 4.41 cm/year in the placebo group (LS mean difference 1.49 cm/year, p<0.0001). Navepegritide was well tolerated, with ∼99% of reported AEs being mild (Grade 1) or moderate (Grade 2). No AEs led to trial withdrawal or treatment discontinuation. Incidence of treatment-related AEs was similar between groups (21.1% with navepegritide vs 25.9% with placebo). There was a low incidence of ISRs in both groups (19.3% or 0.41 events per person year of exposure to navepegritide vs 14.8% or 0.15 with placebo). All ISRs were mild (Grade 1). AEs of asymptomatic hypotension were documented in two participants in each the navepegritide group (3.5%) and the placebo group (7.4%); none were considered treatment-related. Conclusion: In the pivotal ApproaCH trial, navepegritide significantly improved linear growth in children with ACH while maintaining a safety profile comparable to placebo. The treatment was well-tolerated and most TEAEs were mild or moderate. Weekly administration of navepegritide was associated with a low incidence of ISRs and no evidence of treatment-related hypotensive effects. These results suggest that the design of once-weekly navepegritide as a prodrug with a low CNP Cmax contributes to a favorable safety and tolerability profile, and may address limitations of existing ACH therapies and support improved treatment adherence. Presentation: Monday, July 14, 2025
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,002 | 0,002 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,002 | 0,003 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,001 |
| Communication savante | 0,001 | 0,001 |
| Science ouverte | 0,001 | 0,000 |
| Intégrité de la recherche | 0,001 | 0,003 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,006 | 0,001 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».