Fifty-two children with achondroplasia treated at clinics in Argentina, Colombia, Mexico, Chile, Paraguay and Uruguay grew faster on vosoritide, and after roughly a year and a half of treatment their height had climbed more than a full standard deviation up the growth chart. The gain showed up across both sexes and every age group. The body proportions that define the condition did not change at all.
That is the read from EVOLAC, a retrospective real-world study published online August 31 in the American Journal of Medical Genetics Part A ↗. It matters not because the result is surprising, but because of where the data came from: routine practice in six Latin American countries with very different health systems, not the controlled setting of a company trial.
What the study measured
Achondroplasia is the most common form of disproportionate short stature. It comes from a gain-of-function change in the FGFR3 gene, which acts as a brake on the growth plates at the ends of children's bones and leaves them short with a characteristically different body shape. Vosoritide, sold as Voxzogo by BioMarin, is a lab-made copy of C-type natriuretic peptide. It binds a receptor called NPR-B and pushes back on the overactive FGFR3 signal, letting cartilage grow. It was the first drug the FDA ever approved for the condition, in November 2021.
The researchers were led by clinicians at the Hospital Interzonal General de Agudos Eva Perón near Buenos Aires. They pulled records for children with genetically confirmed achondroplasia who had at least six months of vosoritide and two or more growth measurements. The 52 children started treatment at a mean age of 5.9 years. They stayed on the drug, given daily by injection, for a mean of 539 days. Adherence was high: patients spent about 94 percent of the time without an interruption.
Height, expressed as a Z-score (how far a child sits from the average, in standard deviations), rose significantly between 6 and 36 months, from 0.33 to 1.58. In plain terms, the children moved more than a full step up the growth curve relative to where they started. Annualized growth velocity, the speed of growing, jumped most in the first year and then settled toward the rate of children without the condition. Side effects were common but mild, mostly reactions at the injection site. No child had a severe adverse event or stopped for a safety reason. Ninety-eight percent of caregivers said they saw a positive change in their child's well-being or daily functioning, and all of them said they would recommend the treatment.
What it does not settle
The generalizability is the genuine news here. A drug that worked in trial centers also worked in a public hospital in Resistencia and a private practice in Santa Fe, which is not something a controlled study can tell you. But three things sit under the headline.
There was no control group. The children were compared against reference growth curves and against their own pre-treatment velocity. Ordinary regression, and the expectations of families and doctors who chose to keep injecting, are not fully ruled out. The caregiver-reported outcomes are favorable, but they came from an open study with no blinding. That is the setting most prone to a rosy read.
The body-proportion measures stayed flat. Vosoritide added height without touching the disproportion that defines achondroplasia. That is the same limit a pooled analysis of vosoritide and navepegritide ↗ flagged earlier, and the gap that a navepegritide-plus-growth-hormone combination ↗ is trying to close.
Most of all, height is a surrogate. The FDA's 2021 clearance was an accelerated approval based on annualized growth velocity. It was not based on the complications that actually make achondroplasia dangerous: narrowing at the base of the skull, sleep apnea, spinal stenosis, ear infections. EVOLAC measured centimeters and caregiver impressions, not any of those. Whether a taller child is a healthier child, on the outcomes that send families to specialists, is the question this study was not built to answer. It is also the one that still needs answering.