In seven infants with achondroplasia, a once-weekly peptide widened the hole at the base of the skull by an average of 3.15 millimeters over a year. That opening, the foramen magnum, is where the spinal cord leaves the brain, and in achondroplasia it can close in on the cord tightly enough to kill. Height gets the headlines in this disease. The skull base is where the early danger actually sits.
The data came from the open-label sentinel cohort of reACHin, a Phase 2 trial of Ascendis Pharma's navepegritide, presented on September 9 ↗ at the European Society for Paediatric Endocrinology meeting in Marseille by Dr. Genevieve Baujat of Necker-Enfants Malades Hospital in Paris. Navepegritide, also called TransCon CNP, is a slow-release prodrug of C-type natriuretic peptide, or CNP. CNP is the body's own signal that tells the growth plate to grow, and the FGFR3 mutation that causes achondroplasia keeps that signal from working properly. The drug is a version of CNP engineered to release steadily from a single weekly injection instead of clearing in minutes, which is how the natural peptide behaves. It is already approved in the United States as Yuviwel for children two and older. This trial pushed into the age group below that, the first year or two of life, where the drug had not been tested before.
The cohort was small and early: seven treatment-naive infants, average age 11.7 months, all under two years old, followed for 52 weeks. The reason to run a trial in babies this young, despite the obvious caution that requires, is that the foramen magnum problem is an infant problem. Cord compression at the skull base is a leading cause of early death in achondroplasia, and surgery to decompress it is one of the most common major operations these children face in their first years. If a drug is going to help there, it has to be working while the skull base is still forming.
On that specific question the readout was encouraging. The average increase in the front-to-back diameter of the foramen magnum was 3.15 millimeters. A standardized rating called the Achondroplasia Foramen Magnum Score, which grades how narrowed the opening is, was stable or improved in every one of the seven infants. None of them needed decompression surgery during the year. In a condition where that surgery is a real and expected event in this age band, zero operations across a treated cohort is the kind of signal the trial was built to look for, even if seven children is far too few to call it proof.
The growth numbers came along with it. Annualized growth velocity was 9.9 centimeters a year, meaning the infants grew at close to ten centimeters over the twelve months. Their length, measured on an achondroplasia-specific scale that compares them to other children with the condition rather than to average-height children, improved by 0.42 standard deviations, a modest but real upward shift. Growth velocity that high in the first years is partly just how fast babies grow, so the honest read is that the height data support the drug without being the story on their own.
Safety, which matters more than usual when the patients are infants, was clean over the year. There were no injection-site reactions, no fractures or other bone problems, no symptomatic drops in blood pressure (a known theoretical risk with CNP, which relaxes blood vessels), and no deaths. No adverse event was judged related to the drug, and none led anyone to stop treatment.
The caveats are the ones that come with every early trial and then some. This is seven infants, open-label, with no control group, over a single year. The foramen magnum widened, but whether that translates into fewer surgeries and fewer deaths over the years that follow is exactly what an open-label sentinel cohort cannot answer. The data were presented at a conference and released by the company, not yet published with full peer review.
What makes the piece worth running is the shift in what is being measured. Earlier achondroplasia drug data have leaned on the standing-height number because it is easy to measure and easy to sell. The real-world vosoritide results, for instance, showed the drug added height to achondroplastic kids without fixing the disproportion ↗. Height is not what kills a child with achondroplasia in the first two years. A narrow foramen magnum can. Watching a peptide move that specific measurement, in the specific age group where it matters, is a more clinically honest way to ask whether the drug does anything that counts. Whether it holds up is a question for a controlled trial and a longer clock.