Ascendis Pharma’s 104-week ApproaCH trial results show sustained improvements in lower limb alignment and growth in children with achondroplasia treated with once-weekly TransCon CNP (YUVIWEL®), reinforcing its long-term clinical profile.
Written By: Nalam Karthik, PharmD
Reviewed By: Pharmacally Editorial Team
Ascendis Pharma has reported new 104-week data from the pivotal ApproaCH trial (NCT05598320) demonstrating sustained improvements in lower extremity alignment in children with achondroplasia treated with once-weekly TransCon CNP (navepegritide).
The findings, presented at the 12th International Conference on Children’s Bone Health (ICCBH 2026) in Montreal, showed continued reductions in tibial-femoral angle (TFA), a key radiographic measure of leg alignment associated with genu varum (bowed legs).
The latest results build on previously reported improvements in annualized growth velocity and height Z-scores, suggesting that prolonged treatment may improve both skeletal growth and lower limb alignment.
TransCon CNP Targets the Underlying Biology of Achondroplasia
Achondroplasia is the most common form of disproportionate short stature and results from overactive FGFR3 signaling, which disrupts normal bone growth. Beyond reduced height, the condition can cause progressive skeletal deformities, chronic pain, impaired mobility, spinal abnormalities, respiratory complications, and repeated orthopedic surgeries.
TransCon CNP is a once-weekly prodrug that provides continuous exposure to active C-type natriuretic peptide (CNP), counteracting excessive FGFR3 signaling and promoting more proportional skeletal development.
The therapy received U.S. FDA approval in February 2026 under the brand name YUVIWEL® for pediatric patients aged two years and older with achondroplasia and open growth plates. Its European marketing application remains under review.
ApproaCH Trial Demonstrated Progressive Improvement Through Week 104
The randomized, double-blind, placebo-controlled pivotal trial enrolled 84 children aged 2 to 11 years with achondroplasia. Participants received TransCon CNP 100 µg/kg once weekly or placebo for 52 weeks before entering a 52-week open-label extension in which all participants received active treatment.
Radiographic assessments showed that children treated with TransCon CNP from the start of the study experienced continuous improvements in TFA through Week 104. Mean TFA declined from 9.1° at baseline to 6.9° after two years, representing a 2.2° improvement.
Children with preexisting genu varum derived greater benefit. In this subgroup, mean TFA improved from 13.4° to 9.6°, corresponding to a 3.8° reduction over two years.
Participants who switched from placebo to TransCon CNP after Week 52 also demonstrated improvements during the open-label extension. In children with baseline genu varum, TFA improved by 3.8° after initiating active treatment, indicating that skeletal alignment continued to respond even after delayed therapy.
TFA Z-scores improved across treatment groups, further supporting sustained correction of lower limb alignment. Investigators also reported stable fibula-to-tibia length ratios throughout treatment, indicating that improvements occurred alongside proportional lower-leg growth.
Safety Findings Remained Consistent
TransCon CNP maintained a favorable safety profile through two years of treatment. Investigators reported a low incidence of injection-site reactions, all of which were mild, with no cases of symptomatic hypotension or accelerated bone age. Most adverse events were mild to moderate in severity, and none led to treatment discontinuation or withdrawal from the trial. Overall, the findings indicate that prolonged treatment was well tolerated while supporting continued skeletal development.
Clinical Implications and Regulatory Path
Presenting investigator Leanne M. Ward, MD, said the data indicate that continuous CNP exposure may improve both skeletal growth and lower limb alignment, potentially reducing complications that contribute to chronic pain, impaired mobility, and future orthopedic surgery in children with achondroplasia.
Ascendis continues to expand the clinical evidence supporting TransCon CNP beyond linear growth. While the therapy is already approved in the United States as YUVIWEL®, the European Medicines Agency is reviewing the marketing authorization application, with a regulatory decision expected in the fourth quarter of 2026. The new two-year radiographic findings further strengthen the therapy’s long-term clinical profile as treatment shifts toward addressing broader manifestations of achondroplasia rather than height alone.
What This Means for Patients
Children with achondroplasia often develop bowed legs (genu varum), which can cause pain, limit mobility, and increase the need for orthopedic surgery. The new two-year data suggest that once-weekly TransCon CNP not only supports sustained linear growth but also improves lower limb alignment over time, particularly in children who already have leg bowing. The treatment also maintained a favorable safety profile, with no new safety concerns identified during two years of follow-up. Together, these findings indicate that TransCon CNP may help address multiple complications of achondroplasia while supporting healthier skeletal development during childhood.
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About the Writer
Nalam Karthik (LinkedIn) is a healthcare writer and PharmD graduate with interests in pharmacovigilance, drug safety, clinical data analysis, and quality assurance. He is passionate about translating clinical and pharmaceutical knowledge into accessible healthcare content while staying engaged with advancements in drug development and patient safety initiatives.