Ascendis Reports 78-Week Data From COACH Trial for Achondroplasia

Ascendis Pharma A/S has announced week 78 data from the Phase 2 COACH trial investigating combination navepegritide and lonapegsomatropin in adolescent patients with achondroplasia.¹

The August 6 announcement showed durable, unprecedented growth with combination treatment using once-weekly navepegritide (developed as TransCon CNP) and once-weekly lonapegsomatropin (TransCon hGH). According to the announcement, mean annualized growth velocity across both study cohorts met or exceeded the 97th percentile of children of average stature through 78 weeks, without new safety or tolerability signals. Ascendis also reported week 104 data from the pivotal ApproaCH monotherapy trial and provided a commercial update on YUVIWEL (navepegritide), its FDA-approved achondroplasia therapy.¹

“I am excited to see compelling long-term efficacy, safety, and tolerability data for TransCon CNP monotherapy,” Carlos Bacino, MD, professor of molecular and human genetics at Baylor College of Medicine and Texas Children's Hospital, said in a statement. “TransCon CNP has demonstrated positive effects compared to placebo on multiple aspects of skeletal growth, including statistically significant improvements in height and lower-limb alignment, with growing long-term data highlighting its unprecedented efficacy when used in combination with TransCon hGH.”¹

Navepegritide monotherapy, approved by the FDA in February 2026 under the brand name YUVIWEL for pediatric patients 2 years and older with achondroplasia and open epiphyses, remains the only approved agent in the combination regimen; lonapegsomatropin is investigational in achondroplasia and separately approved as SKYTROFA for growth hormone deficiency. The COACH update adds longer-term durability data to the combination approach as Ascendis continues to expand its achondroplasia pipeline across age groups and disease severity.^1,2

Navepegritide-lonapegsomatropin efficacy in the COACH trial

COACH is an ongoing prospective Phase 2 open-label trial evaluating combination treatment with once-weekly navepegritide at 100 µg/kg/week and once-weekly lonapegsomatropin at a starting dose of 0.30 mg/kg/week in children with achondroplasia aged 2 to 11 years. The trial enrolled a navepegritide treatment-naive cohort (n = 12; mean age, 5.26 years) and a previously treated cohort (n = 9; mean age, 8.32 years) with a mean prior navepegritide exposure of 2.56 years. Through week 78, mean annualized growth velocity remained at or above the 97th percentile of children of average stature in both cohorts, consistent with week 26 and week 52 findings.¹

In the treatment-naive cohort, mean annualized growth velocity at week 78 was 7.73 cm/year, with mean achondroplasia height Z-score rising from 0.46 to 1.75, an increase of 1.29. In the CNP-experienced cohort, mean annualized growth velocity was 7.67 cm/year, with height Z-score improving from 1.28 to 2.38, an increase of 1.10. Ascendis reported the magnitude of Z-score improvement represents a tripling of efficacy compared with navepegritide monotherapy alone.¹

Navepegritide monotherapy safety and efficacy in ApproaCH

Children treated with combination therapy showed continued improvement in body proportionality through week 78, tracking with the observed gains in linear growth. Safety and tolerability were consistent with those previously reported for navepegritide and lonapegsomatropin monotherapies, according to Ascendis. Combination therapy was generally well tolerated, with a low incidence of injection site reactions and mostly mild treatment-emergent adverse events.¹

All 21 enrolled children, 100% of the trial population, completed 78 weeks of treatment and remain on therapy. Ascendis said additional week 78 COACH data will be presented at an upcoming medical meeting.¹

In the pivotal ApproaCH trial, week 104 data for navepegritide monotherapy at 100 µg/kg once weekly showed durable gains in annualized growth velocity and height Z-score among children randomized to active treatment, with substantial catch-up improvement among those who switched from placebo at week 52.¹ The monotherapy dataset also demonstrated improved tibial-femoral angle and upper-to-lower body segment ratio, indicating benefits in lower-limb alignment and body proportionality beyond height. Through two years, navepegritide was generally well tolerated, with no symptomatic hypotension and an injection-site reaction rate of 0.35 per person-year of exposure, all mild in severity, and no adverse events led to discontinuation.¹

“We are encouraged to see research on navepegritide continue to examine areas the achondroplasia community has identified as important, including outcomes beyond linear growth,” Mike Hughes, chair of the Biotech Industry Liaison Committee with Little People of America, said in a statement. “The ApproaCH findings add to our understanding of body proportionality and lower-limb alignment, while continued study will be important to determine whether these anatomical changes translate into meaningful differences in function, mobility, or the future need for surgical intervention.”¹

Ascendis has also completed target enrollment for the pivotal reACHin trial, which supports planned regulatory filings for infants younger than 2 years with achondroplasia, and continues to enroll patients in the pivotal teACH trial in adolescents aged 12 to less than 18 years. In the AttaCH long-term extension trial, 96% of 140 enrolled children remain on navepegritide monotherapy or have moved into COACH, with up to nearly six years of follow-up. A decision on the European Marketing Authorisation Application for navepegritide monotherapy is anticipated in the fourth quarter of 2026. On the commercial side, Ascendis reported more than 170 unique YUVIWEL patient enrollments in the United States by approximately 90 prescribing clinicians through June 30, 2026, with more than 65% of patients approved for reimbursement.¹

References

1. Ascendis Pharma A/S. Ascendis announces COACH week 78 results and provides update on achondroplasia programs and YUVIWEL uptake in the U.S. August 6, 2026. Accessed August 6, 2026. https://investors.ascendispharma.com/news-releases/news-release-details/ascendis-announces-coach-week-78-results-and-provides-update

2. Ascendis Pharma A/S. FDA Approves Once-Weekly YUVIWEL (navepegritide) for Children with Achondroplasia Aged 2 Years and Older. February 27, 2026. Accessed August 6, 2026. https://investors.ascendispharma.com/news-releases/news-release-details/fda-approves-once-weekly-yuviwelr-navepegritide-children