Findings from a phase 2 trial showed that once-weekly TransCon CNP plus TransCon hGH produced durable growth and proportionality benefits in children with achondroplasia.
Top-line results from week 52 of the phase 2 COACH trial suggest that combination therapy with once-weekly navepegritide (TransCon CNP) and once-weekly lonapegsomatropin (TransCon hGH) may deliver durable growth benefits in children with achondroplasia without compromising safety or tolerability, according to an announcement from Ascendis Pharma.1
COACH is the first phase 2 clinical trial to evaluate this dual-agent approach, which is designed to address both the underlying biology of achondroplasia and growth promotion. At one year, children treated with the combination exceeded growth benchmarks seen with monotherapy while also demonstrating improvements beyond linear height, including body proportionality and arm span. Safety findings were reported to be consistent with the known profiles of each therapy when used alone.
“The COACH trial has demonstrated unmatched improvements in growth and benefits beyond linear growth without compromising safety or tolerability compared with historical data,” said Ciara McDonnell, MD, FRCPI, consultant in pediatric endocrinology and diabetes at Children’s Health Ireland, in a press release. “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.”
COACH is an ongoing proof-of-concept, prospective, open-label phase 2 study enrolling children aged 2 to 11 years with achondroplasia. Participants received once-weekly navepegritide at 100 µg/kg per week plus once-weekly lonapegsomatropin at a starting dose of 0.30 mg/kg per week.
The study included 2 cohorts: a navepegritide treatment–naive group (n = 12; mean age, 4.67 years) and a cohort previously treated with navepegritide (n = 9; mean age, 7.89 years) who had received navepegritide for a mean of 2.56 years prior to combination therapy. According to the company, the population was representative of children with achondroplasia and reflected the treatment benefit associated with navepegritide.
Growth outcomes at week 52
Among navepegritide-naive children, mean annualized growth velocity (AGV) reached 8.80 cm per year, with a mean improvement in achondroplasia-specific height z score of +1.02 over 52 weeks. Ascendis noted this represented a tripling of efficacy compared with navepegritide monotherapy.
In the cohort previously treated with navepegritide, mean AGV was 8.42 cm per year at week 52, reflecting an increase of 3.28 cm per year from baseline. This group experienced a mean improvement in height z score of +0.86, increasing from 1.28 to 2.15 over one year. Across both cohorts, children treated with combination therapy exceeded the 97th-percentile AGV of average-stature children after 52 weeks.
Benefits beyond linear height
Beyond growth velocity, investigators reported improvements in body proportionality that aligned with gains in linear growth. Arm span improved beyond the 84th percentile of children with achondroplasia at week 52, and bone age remained consistent with chronological age. All children completed 52 weeks of treatment and remained on therapy at the time of the analysis.1
Michael Hughes, chair of the Biotech Industry Liaison Committee at Little People of America, emphasized the relevance of these findings. “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,” Hughes said. “These end points provide important context beyond height alone.”
Combination therapy was generally well tolerated, with a low incidence of injection site reactions and mostly mild treatment-emergent adverse events. The safety profile was consistent with that observed for navepegritide and lonapegsomatropin monotherapies.
Ascendis reported that navepegritide is currently under priority review by the FDA as a monotherapy for children with achondroplasia, with a Prescription Drug User Fee Act (PDUFA) target action date of February 28, 2026. In the fourth quarter of 2025, the company submitted a protocol and completed an End of Phase 2 meeting with the FDA regarding a planned phase 3 trial evaluating the combination regimen in pediatric achondroplasia.
According to previous coverage by Contemporary Pediatrics, navepegritide was evaluated in the phase 2b ApproaCH trial that featured 84 children aged 2 to 11 years in a randomized, double-blind, and placebo-controlled design. The study met its primary end point at week 52, demonstrating a statistically significant improvement in AGV. The least-squares (LS) mean treatment difference was 1.49 cm per year. Investigators reported that “children treated with navepegritide achieved an LS mean AGV of 5.89 vs 4.41 cm/y [cm per year] for those treated with placebo.” The treatment effect emerged by week 12 and was sustained through week 52, with the greatest gains observed among children 8 years or older.2
Navepegritide is currently under regulatory review with the FDA, with a PDUFA date of February 28, 2026, for potential approval.
In our previous coverage of the ApproaCH trial, Carlos A. Bacino, MD, of Baylor College of Medicine in Houston, Texas, discussed the data further in a written Q&A interview.
"Regardless of timing, to me, having navepegritide FDA approved would mean a great addition to the current treatments in achondroplasia,” Bacino said. “We went from solely conservative treatments a few years ago, just addressing medical complications, to treatments that allow us to promote harmonic growth and improvement of known associated complications. In addition, a clear advantage of navepegritide is its weekly dosage.”
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