Combination Navepegritide, Lonapegsomatropin Shows Durable Benefit in Phase 2 Pediatric Achondroplasia Trial

Ascendis Pharma has announced topline results from week 52 of COACH, the first phase 2 clinical trial to evaluate combination therapy with once-weekly navepegritide (TransCon CNP) and once-weekly lonapegsomatropin (TransCon hGH) in children with achondroplasia.1

As described in a January 9, 2026, press release from the Company, at week 52, combination therapy showed durable growth without compromising safety or tolerability, as well as benefits beyond linear growth with improvements in body proportionality and arm span, aligning with the increase in linear growth.1

“The COACH Trial has demonstrated unmatched improvements in growth and benefits beyond linear growth without compromising safety or tolerability compared to historical data,” Ciara McDonnell, MD, a consultant in pediatric endocrinology and diabetes at Children's Health Ireland in Dublin, said in a statement.1 “Seeing the additive effects of these complementary once-weekly therapies, where TransCon CNP makes the growth plates receptive to the growth-promoting effects of TransCon hGH, suggests we may be entering an era where rational dual-agent regimens such as this become a new standard of care in achondroplasia and other growth disorders.”

Navepegritide is an investigational prodrug of C-type natriuretic peptide (CNP) administered once weekly, providing continuous exposure of active CNP to receptors on tissues throughout the body, including growth plates and skeletal muscle. It is under Priority Review by the US Food & Drug Administration (FDA), with an upcoming PDUFA target action date of February 28, 2026.1

Lonapegsomatropin is a prodrug of somatropin administered once weekly, providing sustained release of active, unmodified somatropin. It is investigational in achondroplasia and other indications. In July 2025, it was approved by the FDA for the replacement of endogenous growth hormone in adults with growth hormone deficiency based on results from phase 3 foresiGHt trial.1,2

The efficacy, safety, and tolerability of combined treatment with once-weekly navepegritide at 100 µg/kg/week and once-weekly lonapegsomatropin at a starting dose of 0.30 mg/kg/week is being assessed in the ongoing proof-of-concept prospective phase 2 open-label COACH trial. The study enrolled children with achondroplasia 2-11 years of age and included a cohort of navepegritide treatment-naïve children (n = 12, mean age 4.67 years) and a cohort of navepegritide-treated children (n = 9, mean age 7.89 years), who had received navepegritide (100 µg/kg/week) for a mean of 2.56 years in clinical trials.1

Topline week 52 results showed that in the navepegritide treatment-naïve cohort, mean annualized growth velocity (AGV) was 8.80 cm/year, with an improvement in mean ACH height Z-score of +1.02 over 52 weeks, indicating a tripling of efficacy compared to navepegritide monotherapy. In the navepegritide-treated cohort, mean AGV was 8.42 cm/year, representing an increase from baseline at week 52 of 3.28 cm/year, with an improvement in mean ACH height Z-score of +0.86, increasing from 1.28 to 2.15 over 52 weeks.1

After 52 weeks, children treated with combination therapy exceeded the 97th-percentile AGV of average-stature children. Additionally, results showed children treated with navepegritide and lonapegsomatropin demonstrated improvements in body proportionality after 52 weeks, aligning with the increase in linear growth.1

Further analysis revealed arm span of children treated with combination therapy improved beyond the 84th-percentile of children with achondroplasia at week 52, while bone age remained consistent with chronological age at week 52.1

Of note, safety and tolerability were consistent with those observed for navepegritide and lonapegsomatropin monotherapies, and combination treatment was generally well-tolerated, with a low incidence of injection site reactions and generally mild TEAEs. As described in the release, all children completed 52 weeks of treatment and remain on therapy in the COACH trial.1

“The dwarfism community has long emphasized the importance of research that honors dwarf and disability pride while also deepening understanding of outcomes that matter most in achondroplasia,” said Michael Hughes, Chair of the Biotech Industry Liaison Committee at Little People of America.1 “Although the COACH findings are still early, it is encouraging to see meaningful improvements in arm span and body proportionality alongside changes in linear height, as these endpoints provide important context beyond height alone. Given the diversity of healthcare goals within the dwarfism community, data like these may help expand the range of options individuals and families consider as they weigh what matters most to them.”

References

1. Ascendis. Week 52 COACH Trial Topline Results Confirm Consistent and Durable Treatment Benefits in Children with Achondroplasia (ACH). January 9, 2026. Accessed January 9, 2026. https://investors.ascendispharma.com/news-releases/news-release-details/week-52-coach-trial-topline-results-confirm-consistent-and

2. Brooks A. FDA Approves Lonapegsomatropin-tcgd (Skytrofa), Formerly TransCon hGH, for Adult Growth Hormone Deficiency. HCPLive. July 28, 2025. Accessed January 9, 2026. https://www.hcplive.com/view/fda-approves-lonapegsomatropin-tcgd-skytrofa-formerly-transcon-hgh-for-adult-growth-hormone-deficiency