Academic Journal
Navepegritide combined with lonapegsomatropin for the treatment of children with achondroplasia: 52-week results from the phase 2 COACH trial.
| Τίτλος: | Navepegritide combined with lonapegsomatropin for the treatment of children with achondroplasia: 52-week results from the phase 2 COACH trial. |
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| Συγγραφείς: | McDonnell CM; Department of Endocrinology, Children's Health Ireland at Temple Street, Dublin 1 D01 XD99, Ireland.; Discipline of Paediatrics, University of Dublin, Trinity College, Dublin D02 PN40, Ireland., Irving M; Guy's and St.Thomas' NHS Foundation Trust, Evelina Children's Hospital, London SE1 7EH, United Kingdom., Nolting LA; Department of Pediatrics and Adolescent Medicine, Copenhagen University Hospital, Rigshospitalet, 2100 Copenhagen, Denmark., Abdelrahman SG; Clinical Development, Ascendis Pharma LLC, Palo Alto, CA 94304, United States., Dalby LW; Ascendis Pharma, A/S, 2900 Hellerup, Denmark., Iklé JM; Clinical Development, Ascendis Pharma LLC, Palo Alto, CA 94304, United States., Jensen SM; Ascendis Pharma, A/S, 2900 Hellerup, Denmark., Komirenko AS; Clinical Development, Ascendis Pharma LLC, Palo Alto, CA 94304, United States., Ominsky MS; Clinical Development, Ascendis Pharma LLC, Palo Alto, CA 94304, United States., Shu AD; Clinical Development, Ascendis Pharma LLC, Palo Alto, CA 94304, United States., Hove HB; Department of Pediatrics and Adolescent Medicine, Copenhagen University Hospital, Rigshospitalet, 2100 Copenhagen, Denmark. |
| Πηγή: | European journal of endocrinology [Eur J Endocrinol] 2026 Jun 01; Vol. 194 (6), pp. 745-755. |
| Τύπος έκδοσης: | Journal Article; Clinical Trial, Phase II; Multicenter Study; Randomized Controlled Trial |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Oxford University Press Country of Publication: England NLM ID: 9423848 Publication Model: Print Cited Medium: Internet ISSN: 1479-683X (Electronic) Linking ISSN: 08044643 NLM ISO Abbreviation: Eur J Endocrinol Subsets: MEDLINE |
| Imprint Name(s): | Publication: 2023- : Oxford : Oxford University Press Original Publication: Oslo, Norway : Scandinavian University Press, c1994- |
| Ιατρικοί όροι (MeSH): | Achondroplasia*/drug therapy , Human Growth Hormone*/administration & dosage , Human Growth Hormone*/analogs & derivatives , Human Growth Hormone*/therapeutic use , Natriuretic Peptide, C-Type*/administration & dosage , Natriuretic Peptide, C-Type*/therapeutic use, Humans ; Female ; Child, Preschool ; Male ; Child ; Drug Therapy, Combination ; Treatment Outcome |
| Περίληψη: | Objective: Navepegritide, a prodrug of C-type natriuretic peptide, has demonstrated improved growth and additional benefits, including lower limb alignment, in children with achondroplasia. The well-described mechanism of action of navepegritide in the growth plate is hypothesized to enhance its receptivity to lonapegsomatropin, a prodrug of somatropin, to provide benefits beyond those seen with monotherapies in achondroplasia. Methods: In the proof-of-concept phase 2 COACH trial, children with achondroplasia aged 2 to 11 received weekly navepegritide and lonapegsomatropin. The primary efficacy endpoint was annualized growth velocity (AGV) at week 52 vs AGV with navepegritide monotherapy in the ApproaCH trial (NCT05598320). Results: Twenty-one children were enrolled: 12 received no prior growth-promoting treatment (treatment-naive, TN) and 9 had been receiving navepegritide monotherapy for >1 year (navepegritide-experienced, NE). At week 52, TN children receiving navepegritide and lonapegsomatropin had a least squares mean AGV of 8.69 cm/year versus 5.95 cm/year for matched children who received navepegritide monotherapy, a difference of 2.74 cm/year (P < .0001). Observed mean AGV for TN children was 8.80 cm/year, a +3.89 cm/year increase from baseline (P = .0015). NE children had an observed mean AGV of 8.42 cm/year, a +3.28 cm/year increase from navepegritide-treated baseline (P < .0001). An improvement in body proportionality was observed and arm span increased substantially (+9.4 cm in TN and +7.9 cm in NE children), in line with gains in height. Treatments were well-tolerated with generally mild adverse events and no treatment discontinuations. Conclusions: In this prospective trial, the robust growth and anthropometric results suggest that by continuously relieving the pre-hypertrophic block in achondroplasia, navepegritide may make the growth plate more responsive to the strong complementary effect of lonapegsomatropin. Trial Registration Details: ClinicalTrials.gov NCT06433557. (© The Author(s) 2026. Published by Oxford University Press on behalf of European Society of Endocrinology.) |
| Competing Interests: | Conflicts of interest: Financial arrangements of the authors with companies whose products may be related to this presentation are listed as declared by the authors: C.M.M.: Research support/clinical trial investigator and consultant for Ascendis Pharma. M.I., H.B.H.: Research support/clinical trial investigator and consultant for Ascendis Pharma. L.A.N.: Advisory board: Ascendis Pharma. Research support/clinical trial investigator for Ascendis Pharma. S.G.A., L.W.D., J.M.I., S.M.J., A.S.K., M.S.O., A.D.S. are employed by and may hold stock in Ascendis Pharma. |
| Grant Information: | Ascendis Pharma, Inc. |
| Contributed Indexing: | Keywords: C-type natriuretic peptide; TransCon CNP; TransCon hGH; achondroplasia; growth hormone; lonapegsomatropin; navepegritide |
| Molecular Sequence: | ClinicalTrials.gov NCT05598320; NCT06433557 |
| Substance Nomenclature: | 12629-01-5 (Human Growth Hormone) 127869-51-6 (Natriuretic Peptide, C-Type) OP35X9610Y (lonapegsomatropin) |
| Entry Date(s): | Date Created: 20260518 Date Completed: 20260716 Latest Revision: 20260716 |
| Update Code: | 20260717 |
| DOI: | 10.1093/ejendo/lvag082 |
| PMID: | 42144862 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1479-683X |
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| DOI: | 10.1093/ejendo/lvag082 |