Topline at 52 weeks from Ascendis’ Phase 2 COACH study in pediatric achondroplasia showed mean annualized growth velocity of 8.80 cm/year in the TransCon CNP–naïve cohort (N=12) with an improvement in achondroplasia height Z-score of +1.02, and 8.42 cm/year in the prior TransCon CNP–treated cohort (N=9), a 3.28 cm/year increase from baseline with a +0.86 Z-score gain. Children on combination therapy exceeded the 97th-percentile AGV of average-stature peers. Beyond linear growth, investigators reported improved body proportionality and arm span, with arm span surpassing the 84th percentile for children with achondroplasia, and bone age remaining aligned with chronological age. The once-weekly TransCon CNP plus once-weekly TransCon hGH regimen was generally well tolerated with mostly mild TEAEs, consistent with each agent’s monotherapy experience; all patients completed 52 weeks and remain on treatment.
The core event is the first 52-week readout of a dual-agent regimen combining a CNP prodrug (navepegritide) and a long-acting hGH prodrug (lonapegsomatropin) in children 2–11 years old, assessed in an open-label, two-cohort Phase 2 design. Dosing was TransCon CNP 100 µg/kg/week with TransCon hGH initiated at 0.30 mg/kg/week. Ascendis is concurrently advancing TransCon CNP monotherapy through U.S. FDA Priority Review with a February 28, 2026 PDUFA date and EMA review, while TransCon hGH is approved as SKYTROFA for growth hormone deficiency but remains investigational in achondroplasia. The company submitted a Phase 3 protocol and held an end-of-Phase 2 meeting with FDA in Q4 2025 to discuss a pivotal combination trial.
Strategically, Ascendis is positioning TransCon CNP as a backbone therapy that addresses FGFR3 pathway overactivation, with add-on hGH to amplify growth plate response. The weekly–weekly cadence is a clear bid to differentiate against daily CNP analogs and legacy off-label GH use, and to expand the value story beyond centimeters by highlighting proportionality and arm-span gains. The company cites a “tripling” of efficacy versus its historical TransCon CNP monotherapy Z-score data, but the current evidence is open-label, small, and internally benchmarked—an expected bridge signal, not a registration standard. The pivotal question is whether a randomized dataset can demonstrate clinically meaningful incremental benefit over CNP alone that justifies added cost, monitoring, and potential safety liabilities associated with hGH.
For sites and CROs, a Phase 3 program will hinge on operational rigor in pediatric anthropometrics: standardized stadiometry, proportionality indices, arm-span protocols, and centralized bone age reads to satisfy regulators and HTAs that benefits extend beyond height. Weekly injections are feasible within typical clinic and home-support models, and the 100% completion in this small cohort suggests caregiver acceptance; scaling to larger, older, and more diverse populations will test adherence and retention. Safety surveillance will need to explicitly track GH-associated risks—accelerated bone maturation, intracranial hypertension, orthopedic events, and sleep-disordered breathing—while documenting that proportionality gains translate into functional outcomes that matter to families and payers.
What to watch next is the Phase 3 design and comparator strategy. An add-on study versus TransCon CNP monotherapy would most directly inform a label expansion if CNP is approved; inclusion of an active external comparator such as vosoritide would strengthen payer arguments but adds complexity. Regulatory sequencing will matter: monotherapy approval and any postmarketing commitments could set requirements for the combination path. Durability beyond one year, consistency across age strata, and long-term skeletal safety will be decisive. If a controlled trial confirms proportionality and functional benefits alongside sustained AGV without bone age acceleration, sponsors may have a pathway to a dual-agent standard in achondroplasia; absent that, the field will likely default to simpler single-agent regimens aligned with reimbursement and day-to-day site execution.
Jon Napitupulu is Director of Media Relations at The Clinical Trial Vanguard. Jon, a computer data scientist, focuses on the latest clinical trial industry news and trends.
