Navepegritide shows early safety and growth signals in infants with achondroplasia

Once-weekly navepegritide (TransCon CNP), already approved for children 2

years and older with achondroplasia, may also benefit the youngest patients with the condition, according to new data. Week 52 findings from the open-label sentinel cohort of the phase 2 reACHin trial showed stable or improved foramen magnum stenosis—a skull-base narrowing that can compress the brainstem and spinal cord—along with gains in linear growth, in infants aged 0 to younger than 2 years with genetically confirmed achondroplasia. The data were presented by Geneviève Baujat, MD, a clinical geneticist at Necker-Enfants Malades Hospital in Paris, at the 2026 annual meeting of the European Society for Paediatric Endocrinology.

“The impressive safety profile and data from this sentinel group show how early intervention with weekly [navepegritide] treatment could help address medical complications and growth limitations in infants with achondroplasia,” Baujat said, noting that the foramen magnum improvement addresses a major safety concern in this population.

reACHin trial design and sentinel cohort in infants with achondroplasia

ReACHin is a phase 2, randomized, placebo-controlled trial evaluating once-weekly navepegritide at 100 μg/kg/week in at least 66 treatment-naive infants aged 0 to younger than 2 years, followed by a 52-week open-label extension. Before the double-blind portion began enrolling, an open-label sentinel cohort of 7 infants (mean age, 11.7 months) was studied to characterize safety and pharmacokinetics in this younger age group.

Efficacy and safety findings from the reACHin sentinel cohort

At Week 52, the Achondroplasia Foramen Magnum Score was stable or improved in all 7 infants, and mean sagittal diameter of the foramen magnum increased by 3.15 mm; no infant required decompression surgery. Linear growth also improved, with a mean change in achondroplasia-specific supine length z score of +0.42 and a mean annualized growth velocity of 9.9 cm/year. Pharmacokinetic exposure was comparable to that in older children, supporting the same weight-based dose. No injection site reactions occurred over 52 weeks, and there were no deaths, fractures, bone-related events, or symptomatic hypotension; no adverse event was judged treatment-related or led to treatment disruption.

Disease burden and unmet need in infants with achondroplasia

Achondroplasia, caused by a gain-of-function variant in FGFR3, affects an estimated 250,000 people worldwide and extends well beyond short stature. In infancy, it can cause spinal abnormalities, enlarged brain ventricles, hearing deficits, airway obstruction, sleep-disordered breathing, hip problems, and chronic pain, and foramen magnum stenosis carries a risk of serious neurologic compromise. Disease-modifying options have so far been limited to children 2 years and older, leaving a gap during the period when some complications first appear.

Navepegritide mechanism and prior approvals in achondroplasia

Navepegritide is a prodrug of C-type natriuretic peptide designed to sustain receptor exposure throughout the body, counteracting overactive FGFR3 signaling. The FDA granted accelerated approval to navepegritide (Yuviwel) in February 2026 for children 2 years and older with open epiphyses, based on 3 randomized, double-blind, placebo-controlled trials, including the pivotal ApproaCH trial, plus up to 3 years of open-label extension data. In ApproaCH, navepegritide produced significantly higher annualized growth velocity than placebo at Week 52, with improved body proportionality and limb alignment. Use in children under 2 remains investigational, and an EMA decision on the existing pediatric indication is expected in the fourth quarter of 2026.

Expert interpretation of the infant safety and efficacy data

The consistency of pharmacokinetic and growth findings with those in older children is reassuring, and the absence of injection site reactions or bone-related events is notable. But the sentinel cohort was small, open-label, and uncontrolled, so the foramen magnum findings—encouraging in a population where stenosis can be life-threatening—cannot yet be attributed definitively to treatment.

Limitations and next steps

These results come from just 7 infants in an unblinded, single-arm cohort, and the trial's double-blind portion will be needed to confirm a true treatment effect. Longer follow-up also matters, since achondroplasia-related complications evolve over childhood and the surrogate endpoints used here have not yet been linked to long-term functional outcomes in infants.

References

1. Ascendis Pharma. First infant data from Ascendis trial of once-weekly TransCon CNP (navepegritide) presented at ESPE 2026. News release. Published September 9, 2026. Accessed September 9, 2026. https://www.biospace.com/press-releases/first-infant-data-from-ascendis-trial-of-once-weekly-transcon-cnp-navepegritide-presented-at-espe-2026

2. Ascendis Pharma. FDA approves once-weekly YUVIWEL (navepegritide) for children with achondroplasia aged 2 years and older. News release. Published February 27, 2026. Accessed September 9, 2026. https://investors.ascendispharma.com/news-releases/news-release-details/fda-approves-once-weekly-yuviwelr-navepegritide-children

3. Savarirayan R, McDonnell C, Bacino CA, et al. Once-weekly navepegritide in children with achondroplasia: the ApproaCH randomized clinical trial. JAMA Pediatr. 2026;180(1):18-25. doi:10.1001/jamapediatrics.2025.4771