Ascendis Pharma Achieves Two-Year Pivotal Data for TransCon CNP in Achondroplasia Ahead of NDA Positioning

Two years of controlled data from Ascendis Pharma's pivotal ApproaCH Trial now underpin the regulatory dossier for navepegritide (TransCon CNP), sharpening the submission timeline for QA and regulatory teams preparing for a potential NDA filing in achondroplasia.

The trial enrolled 84 children aged 2–11 years in a randomized, double-blind, placebo-controlled design, with 53 participants aged ≥5 years at enrollment. In that subgroup, once-weekly TransCon CNP (100 µg/kg) produced an annualized growth velocity (AGV) LS mean of 5.79 cm/year at Week 52 versus 4.02 cm/year for placebo, a treatment difference of +1.78 cm/year (95% CI: 1.22–2.33; p<0.0001). Through Week 104, following placebo crossover to active treatment at the open-label extension, observed mean AGV in the crossover arm converged to 5.53 cm/year, consistent with the active arm's 5.71 cm/year.

ACH-specific height Z-scores in the ≥5-year subgroup improved by +0.75 from baseline at Week 104 (observed mean) in the TransCon CNP arm, against +0.46 in the crossover arm. CDC-based height Z-scores followed a parallel trajectory: +0.58 versus +0.36 at Week 104. These proportionality metrics carry weight for labeling negotiations, where regulators typically scrutinize whether growth gains reflect skeletal normalization rather than simple linear acceleration.

The safety profile through two years remained consistent with the overall population. Injection site reactions were all mild, no symptomatic hypotension was observed, and bone age acceleration, a sentinel concern in pediatric endocrine programs under 21 CFR Part 312 long-term safety monitoring, was absent. No adverse event led to treatment discontinuation or trial withdrawal, a clean dataset that reduces the likelihood of a clinical hold or labeling restriction during review.

For manufacturing and supply-chain leads, the convergence of crossover-arm AGV toward active-arm levels at Week 104 signals that demand modeling for a commercial launch should account for a broad pediatric age range, not a narrow early-treatment window. Rare disease biologics with once-weekly subcutaneous dosing profiles carry specific cold-chain and unit-dose packaging requirements that typically require process validation activities well ahead of a PDUFA date.

The Week 104 subgroup data were presented in part by M. Jennifer Abuzzahab, M.D. at the Pediatric Endocrine Society annual meeting (PES 2026); additional treatment-difference analyses not shown at PES are included in the company's current data release.

The completeness of the two-year dataset, including proportionality endpoints and an uninterrupted safety record, positions the ApproaCH package as a submission-ready evidence base against which FDA reviewers will assess the benefit-risk profile for the full pediatric achondroplasia population.

Source: Ascendis Pharma A/S via GlobeNewswire, May 6, 2026.