Navepegritide (Yuviwel®) for Children with Achondroplasia: New Drugs and Therapeutics

Written by Anna Ryabets-Lienhard, DO

Edited by Neha Patel, DO and Emily Breidbart, MD

On February 27th, 2026, the FDA approved Navepegritide (Yuviwel®), a C-natriuretic peptide (CNP) analog prodrug developed by Ascendis Pharmaceuticals using TransCon® CNP technology.1 The once‑weekly subcutaneous therapy is indicated to promote linear growth in children aged 2 years and older with achondroplasia and open epiphyses. This approval offers an alternative to the daily injectable Vosoritide (Voxzogo®), which was approved in 2021. Navepegritide was authorized under the FDA’s Accelerated Approval Program based on increased annualized growth velocity (AGV), with continued approval contingent on confirmatory trials demonstrating long-term clinical benefit and safety.1

Navepegritide provides sustained CNP exposure over a weekly dosing interval, allowing continuous inhibition of the overactive FGFR3-MAPK signaling that limits endochondral bone growth in achondroplasia.2-4 By counteracting this pathway, CNP supports chondrocyte proliferation and skeletal bone growth.

Navepegritide is supplied as a lyophilized powder in single‑dose vials (1.3 mg, 2.8 mg, and 5.5 mg) that require reconstitution before subcutaneous injection. It is administered once weekly with weight-based dosing per the FDA-approved prescribing information.1 The dose may be given up to two days before or after the scheduled date, ensuring at least five days between injections; if more than two days have passed, the dose should be skipped.1

The accelerated approval is supported by the phase 2b APPROACH trial (NCT05598320), which enrolled 84 treatment-naïve children aged 2 to 11 years with genetically confirmed achondroplasia. 4 At 52 weeks, navepegritide 100 mcg/kg weekly increased annualized growth velocity to 5.89 cm/year vs. 4.41 cm/year with placebo, a least-squares (LS) mean difference of 1.49 cm/year (95% CI: 1.05 –1.93; P < 0.001).4 When broken down by age, children 2 to <5 years treated with navepegritide (n=21) had an LS mean AGV of 6.07 cm/year at week 52, compared with 5.06 cm/year in the placebo group (n=10), an LS mean difference of 1.02 cm/year (p = 0.0084). In children aged 5–11 years, those who received navepegritide (n=36) showed an LS mean AGV of 5.79 cm/year at week 52, compared with 4.02 cm/year in the placebo group (n=17), an LS mean difference of 1.78 cm/year (p < 0.0001). 4 Height Z‑scores also improved, along with measures of lower extremity alignment, fibula-tibial ratios, and physical functioning in younger children. The upper to lower body segment ratio showed nonsignificant difference.4 Participants have continued into an open-label extension study.

The most common adverse reactions (≥5%) with navepegritide 100mcg/kg/week included vomiting, transient injection‑site reactions (swelling, erythema, bruising), extremity pain, and nausea; hypertrichosis also occurred in 3% of participants.1,4,5 No treatment-related serious adverse events, such as symptomatic hypotension, fractures, or death, were reported.4 Although transient blood pressure decreases have been observed with CNP analogs, the label advises only symptom monitoring (i.e., dizziness, fatigue) and does not recommend pre-dose hydration or food intake, unlike vosoritide.1,6 Routine monitoring involves periodic assessment of growth, as well as weight-based dose adjustments. The medication should be discontinued once bone age displays epiphyseal closure. Navepegritide is not recommended for patients with moderate or severe renal impairment (eGFR <60 mL/min/1.73 m²).1

References:

  1. Prescribing Information for Navepegritide (Yuviwel®). Initial US approval 2026. Yuviwel Prescribing Information (USPI).pdf
  2. Ozasa A, Komatsu Y, Yasoda A, Miura M, Sakuma Y, Nakatsuru Y, Arai H, Itoh N, Nakao K. Complementary antagonistic actions between C-type natriuretic peptide and the MAPK pathway through FGFR-3 in ATDC5 cells. Bone. 2005 Jun;36(6):1056-64.
  3. Agoston H, Khan S, James CG, Gillespie JR, Serra R, Stanton LA, Beier F. C-type natriuretic peptide regulates endochondral bone growth through p38 MAP kinase-dependent and -independent pathways. BMC Dev Biol. 2007 Mar 20;7:18.
  4. Savarirayan R, McDonnell C, Bacino CA, Hoernschemeyer DG, Legare JM, Abuzzahab MJ, Hofman PL, Campeau PM, de Bergua Domingo JM, Ward LM, Smit K, Smith A, Mao M, Ominsky MS, Freiberg LC, Shu AD, Hove HB. Once-Weekly Navepegritide in Children With Achondroplasia: The APPROACH Randomized Clinical Trial. JAMA Pediatr. 2026 Jan 1;180(1):18-25. (on-line version reflects corrections)
  5. Savarirayan, Ravi et al. Once-weekly TransCon CNP (navepegritide) in children with achondroplasia (ACcomplisH): a phase 2, multicentre, randomised, double-blind, placebo-controlled, dose-escalation trial. eClinicalMedicine, Volume 65, 102258
  6. Prescribing Information for Vosoritide (Voxzogo®). Initial US approval 2021. Update 10/2023. label
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