TransCon CNP shows sustained growth gains in children 5 years and older with achondroplasia

New 2-year data from the pivotal ApproaCH trial demonstrated sustained improvements in growth outcomes among children 5 years and older with achondroplasia treated with once-weekly TransCon CNP (navepegritide), according to a May 6, 2026, announcement from Ascendis Pharma.

The subgroup analysis included children 5 years and older at enrollment who received TransCon CNP during the randomized, placebo-controlled portion of the study and the subsequent open-label extension. Investigators reported significantly greater annualized growth velocity (AGV) at week 52 compared with placebo, with improvements sustained through 2 years of treatment.

“These results, along with the improved skeletal alignment and body proportionality and positive changes in health-related quality of life previously reported for the overall population, further highlight TransCon CNP’s ability to promote healthy, proportional growth in children with achondroplasia across age groups,” said Aimee D. Shu, MD, executive vice president of endocrine and rare disease medical science and chief medical officer at Ascendis Pharma.

How was the ApproaCH trial designed?

The ApproaCH trial enrolled 84 children aged 2 to 11 years with achondroplasia. Participants were randomly assigned to receive once-weekly TransCon CNP at 100 µg/kg or placebo for 52 weeks, followed by a 52-week open-label extension in which all participants received active therapy through week 104. Fifty-three participants were 5 years or older at enrollment.

What growth outcomes were reported with TransCon CNP?

At week 52, children aged 5 years and older treated with TransCon CNP achieved a least squares mean AGV of 5.79 cm/year compared with 4.02 cm/year in the placebo group, representing a treatment difference of 1.78 cm/year (95% CI, 1.22-2.33; P < .0001). Observed mean AGV values were 5.84 cm/year with TransCon CNP and 3.88 cm/year with placebo, corresponding to a treatment difference of 1.97 cm/year (95% CI, 1.37-2.56; P < .0001).

Growth improvements were maintained through week 104. Among children initially assigned to TransCon CNP, observed mean AGV at week 104 was 5.71 cm/year, while children who crossed over from placebo to active treatment achieved 5.53 cm/year.

Investigators also reported improvements in height z-scores. At week 52, the least squares mean change from baseline in achondroplasia-specific height z-score was +0.38 in the TransCon CNP group vs +0.07 in the placebo group. The treatment difference was +0.31 (95% CI, 0.20-0.42; P < .0001). Similar gains were observed using CDC-based height z-scores.

By week 104, children receiving continuous TransCon CNP therapy demonstrated sustained gains in both achondroplasia-specific and CDC-based height z-scores.

“We are pleased to see confirmation of the expected sustained growth improvements in these children, with a consistent safety and tolerability profile,” Shu said.

What safety findings were observed through 2 years?

The safety profile through 2 years of treatment in children 5 years and older was reported to be similar to the overall study population. Investigators noted a low rate of injection site reactions, all of which were mild, with no symptomatic hypotension and no acceleration of bone age. Most adverse events were mild or moderate, and none led to treatment discontinuation or withdrawal from the trial.

What is TransCon CNP and how does it work in achondroplasia?

TransCon CNP is a once-weekly prodrug of C-type natriuretic peptide designed to provide continuous exposure of active peptide to counteract overactive FGFR3 signaling in achondroplasia. The therapy received FDA approval in February 2026 under the trade name Yuviwel for increasing linear growth in pediatric patients 2 years and older with achondroplasia and open epiphyses.²

Achondroplasia is a rare genetic condition associated with abnormal FGFR3 signaling and is estimated to affect more than 250,000 individuals worldwide. The condition is associated with skeletal abnormalities and systemic complications that may affect neurologic, respiratory, musculoskeletal, and quality-of-life outcomes across the lifespan.

References

1. New 2-year data from pivotal ApproaCH trial of TransCon CNP (navepegritide) show pronounced gains in growth outcomes in children with achondroplasia aged ≥5 years. News release. Ascendis Pharma. May 6, 2026. Accessed May 6, 2026. https://investors.ascendispharma.com/news-releases/news-release-details/new-2-year-data-pivotal-approach-trial-transconr-cnp

2. FDA approves once-weekly Yuviwel (navepegritide) for children with achondroplasia aged 2 years and older. News release. Ascendis Pharma. February 27, 2026. Accessed May 6, 2026. https://investors.ascendispharma.com/news-releases/news-release-details/fda-approves-once-weekly-yuviwelr-navepegritide-children