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PEGylated C-type natriuretic peptide prodrug

Navepegritide

Navepegritide (TransCon CNP, Yuviwel) is a once-weekly prodrug of a C-type natriuretic peptide analogue: CNP(1-38) attached to a PEG carrier through a cleavable linker, giving continuous CNP exposure to counteract over-active FGFR3 signalling in achondroplasia.

By The Peptides Codex Editorial TeamReviewed September 7, 2026

Page data last changed: . Chemistry registry snapshot: . Registry refreshes and identity assessments are separate from scientific content review.

Length
38 aa
Class
PEGylated C-type natriuretic peptide prodrug
Function
Sustained release of a CNP analogue to counterbalance over-active FGFR3 signalling in growth plates
Context
Approved (FDA accelerated approval, February 2026) to increase linear growth in children ≥2 years with achondroplasia and open epiphyses

The first once-weekly CNP therapy for achondroplasia — a prodrug that keeps CNP exposure continuous.

Also known as: TransCon CNP · Yuviwel · CNP(1-38) prodrug

Part of the Growth hormone & IGF peptides cluster

Overview

Navepegritide (TransCon CNP, Yuviwel) is a once-weekly prodrug of a C-type natriuretic peptide analogue: CNP(1-38) attached to a PEG carrier through a cleavable linker, giving continuous CNP exposure to counteract over-active FGFR3 signalling in achondroplasia. It received FDA accelerated approval in February 2026 for children aged 2 and older with achondroplasia and open growth plates, on the strength of the phase 2b APPROACH trial (Savarirayan et al., JAMA Pediatrics 2026).

Source & context

Biological / chemical source: CNP(1-38) analogue attached to an inert polyethylene glycol carrier via a cleavable linker

Primary research or clinical context: Approved (FDA accelerated approval, February 2026) to increase linear growth in children ≥2 years with achondroplasia and open epiphyses

What navepegritide is

Navepegritide, developed by Ascendis Pharma as TransCon CNP and marketed as Yuviwel, is a prodrug of a human C-type natriuretic peptide (CNP) analogue. It comprises CNP(1-38) attached to an inert polyethylene glycol carrier through a cleavable linker, designed to release the active peptide slowly so that CNP exposure is continuous across a once-weekly injection (IUPHAR record). CNP is a validated therapeutic target in achondroplasia; the approved analogue vosoritide, which is on this site, delivers it once daily. Navepegritide's design goal is the same biology with weekly dosing and no exposure trough.

Mechanism: CNP against FGFR3

Achondroplasia is caused by activating mutations in FGFR3, which suppress endochondral ossification in the growth plates of long bones and produce disproportionate short stature and multisystem complications (Legare & Modaff, GeneReviews; Zakheim et al., Molecular and Cellular Pediatrics 2025). CNP signalling through its receptor opposes the FGFR3 pathway downstream, so continuous CNP exposure is proposed to counterbalance the over-activated signal and restore growth velocity (IUPHAR record; Kang, Drugs 2026). The vosoritide profile explains the same mechanism from the perspective of the first approved CNP analogue.

Phase 2: ACcomplisH

ACcomplisH was a global, randomised, double-blind, placebo-controlled, dose-escalation phase 2 trial in prepubertal children aged 2–10 with genetically confirmed achondroplasia, randomised 3:1 to once-weekly subcutaneous TransCon CNP at 6, 20, 50 or 100 µg CNP/kg/week or placebo for 52 weeks (Savarirayan et al., EClinicalMedicine 2023). Forty-two participants received active drug and 15 placebo. Treatment-emergent adverse events were mild or moderate with no grade 3/4 events; two serious events were assessed as unrelated; 11 injection-site reactions occurred in 8 participants; no symptomatic hypotension occurred. Growth velocity improved dose-dependently, and at 52 weeks the 100 µg/kg/week dose significantly improved annualised growth velocity versus placebo (least-squares mean 5.42 cm/year, 95% CI 4.74–6.11, versus the placebo value).

Phase 2b: APPROACH, the pivotal trial

APPROACH enrolled 84 children aged 2 to 11 with genetically confirmed achondroplasia, naive to growth-promoting treatment, at 10 hospitals in Australia, Canada, Denmark, Ireland, New Zealand, Spain and the US, and randomised them to navepegritide 100 µg/kg/week or placebo by once-weekly subcutaneous injection, with blinded treatment through 52 weeks and an ongoing open-label extension (Savarirayan et al., JAMA Pediatrics 2026). The primary endpoint was annualised growth velocity at week 52; secondary measures included radiographic skeletal outcomes and health-related quality of life. All 84 enrolled participants were analysed for safety and efficacy, including two who discontinued. The trial is described as pivotal, and the FDA's accelerated approval followed in February 2026.

Navepegritide trials in achondroplasia
TrialDesignParticipantsDoseDuration
ACcomplisH (NCT04085523)Phase 2, dose escalation, placebo-controlled57 (42 active, 15 placebo), ages 2–106 / 20 / 50 / 100 µg CNP/kg/week52 weeks
APPROACH (NCT05598320)Phase 2b pivotal, placebo-controlled84, ages 2–11100 µg/kg/week52 weeks + open-label extension

Regulatory status as of September 2026

Navepegritide received accelerated approval in the USA in February 2026 to increase linear growth in paediatric patients aged 2 years and older with achondroplasia and open epiphyses (Kang, Drugs 2026; IUPHAR clinical-use record). It is also being investigated for hypochondroplasia, and ClinicalTrials.gov lists recruiting phase 2 trials in adolescents and additional placebo-controlled studies. Accelerated approval is conditional on confirmatory evidence; readers should consult the current label for the approved population. This page is educational, not treatment guidance.

How it relates to other peptides on this site

Vosoritide is the first approved CNP analogue, given daily; navepegritide applies the same TransCon prodrug technology used in palopegteriparatide (PTH) to CNP for weekly dosing. The CNP profile covers the endogenous hormone. Reviews in the evidence pack place navepegritide among the emerging precision therapies for achondroplasia alongside vosoritide and the tyrosine kinase inhibitor infigratinib (Taylor-Miller et al., Expert Review of Endocrinology & Metabolism 2024).

Structure & chemistry

Molecular identity & reference confidence

Reference mass unavailable

Reference values are taken from the cited molecular record or curated profile. A database match is not independent laboratory verification; modifications, counter-ions, and formulations can change the measured mass.

Molecular form
C-type natriuretic peptide (1-38) analogue, PEGylated through a cleavable linker
Species
Not established by this molecular identity audit
Termini (N / C)
Not specified / Not specified

Average reference mass

Reference policy updated: 2026-10-05

Receptors
Natriuretic peptide receptor B (NPR-B) via released CNP analogue
Backbone
C-type natriuretic peptide (1-38) analogue, PEGylated through a cleavable linker
Status
Approved: FDA accelerated approval (February 2026), achondroplasia in children ≥2 years with open epiphyses; under investigation in hypochondroplasia
Identifiers

Chemistry values: curated profile, IUPHAR/BPS Guide to Pharmacology · fetched 2026-09-07.

Clinical development snapshot

ClinicalTrials.gov lists 5 registered studies with “Navepegritide” as an intervention (snapshot 2026-09-07). A registry footprint is not evidence of efficacy or approval.

Registered studies
5
Highest phase reached
Phase 3
Active in latest 100
3
Most recent update
2026-07-14
Most recently updated studies
NCTTitlePhaseStatusUpdated
NCT05598320A Clinical Trial to Evaluate Efficacy and Safety of TransCon CNP Compared With Placebo in Children With AchondPhase 3completed2026-07-14
NCT04085523A Dose Escalation Trial Evaluating Safety, Efficacy, and Pharmacokinetics of TransCon CNP Administered Once WePhase 2completed2026-07-02
NCT06732895A Clinical Trial to Evaluate Efficacy and Safety of Navepegritide in Adolescents (12 - 18 Years of Age) With APhase 2recruiting2026-04-21
NCT06079398A Clinical Trial to Evaluate Efficacy and Safety of TransCon CNP Compared With Placebo in Infants (0 to <2 YeaPhase 2recruiting2026-04-08
NCT06433557A Phase 2 Clinical Trial to Evaluate Efficacy, Safety, and Tolerability of Navepegritide in Combination With LPhase 2active not recruiting2026-02-18
See all on ClinicalTrials.gov →

Change log

Dated observations from the data pipeline (registry flags, trial footprints, identifiers) and editorial reviews of this profile.

  1. IdentifiersCross-linked to IUPHAR ligand 14293.
  2. TrialsClinicalTrials.gov snapshot added: 5 registered studies, highest phase 3.
  3. EditorialProfile content reviewed and updated by the editorial team.

FAQ about Navepegritide

What is Navepegritide?+

Navepegritide (TransCon CNP, Yuviwel) is a once-weekly prodrug of a C-type natriuretic peptide analogue: CNP(1-38) attached to a PEG carrier through a cleavable linker, giving continuous CNP exposure to counteract over-active FGFR3 signalling in achondroplasia. It received FDA accelerated approval in February 2026 for children aged 2 and older with achondroplasia and open growth plates, on the strength of the phase 2b APPROACH trial (Savarirayan et al., JAMA Pediatrics 2026).

What Canadian product status is recorded for Navepegritide?+

Canadian product status for Navepegritide has not been verified in this profile. No verified record here does not mean no authorization exists. Status depends on the product, formulation and use; consult Health Canada's product records.

What is the typical length of Navepegritide?+

Navepegritide is commonly described as approximately 38 amino acids (PEGylated C-type natriuretic peptide prodrug).

What is navepegritide?+

A once-weekly prodrug of a C-type natriuretic peptide analogue (CNP(1-38) on a PEG carrier with a cleavable linker) developed by Ascendis Pharma for achondroplasia, marketed as Yuviwel.

Is navepegritide approved?+

Yes — FDA accelerated approval in February 2026 for children aged 2 and older with achondroplasia and open growth plates.

How does navepegritide differ from vosoritide?+

Both deliver CNP signalling to counter FGFR3 over-activity. Vosoritide is dosed once daily; navepegritide is a prodrug designed for continuous CNP exposure with once-weekly injection.

What did the trials show?+

In ACcomplisH, 100 µg/kg/week improved annualised growth velocity versus placebo at 52 weeks (5.42 cm/year) with mild-to-moderate adverse events; the pivotal APPROACH trial (84 children) used the same dose with growth velocity at week 52 as the primary endpoint.

Is navepegritide used in adults?+

No. The approval is for children with open epiphyses; trials in adolescents and in hypochondroplasia are ongoing.

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References & further reading

  1. 1.Savarirayan R et al. (2026). Once-Weekly Navepegritide in Children With Achondroplasia: The APPROACH Randomized Clinical Trial. JAMA Pediatr
  2. 2.Savarirayan R et al. (2023). Once-weekly TransCon CNP (navepegritide) in children with achondroplasia (ACcomplisH): a phase 2, multicentre, randomised, double-blind, placebo-controlled, dose-escalation trial. EClinicalMedicine
  3. 3.Kang C (2026). Navepegritide: First Approval. Drugs
  4. 4.Taylor-Miller T et al. (2024). Progress in managing children with achondroplasia. Expert Rev Endocrinol Metab
  5. 5.Zakheim E et al. (2025). Achondroplasia treatments in children aged 5 and older. Mol Cell Pediatr
  6. 6.Legare JM, Modaff P. Achondroplasia. GeneReviews (updated 2026)
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