Growth hormone works in Turner syndrome: it improves height and has been part of standard care since childhood. The problem is less the molecule than the routine. Seven injections a week for years on end, often given by a mother or father before school, is a burden that shows up in daily life and, when it slips, undermines results. That is why drugmakers have spent years looking for long-acting versions. Lonapegsomatropin is one of them: a prodrug given once a week that releases somatropin steadily into the body.
Before asking whether that weekly schedule works as well as the daily one, there is an earlier question that tends to be pushed into the background: how much hormone belongs in each injection. That is what the New InsiGHTS trial set out to answer. It is a phase 2, dose-ranging study, registered as NCT05690386 and run at 19 centres in the United States, in which 49 prepubertal children with Turner syndrome took part. They were randomly assigned in four equal groups: three received weekly lonapegsomatropin at 0.24, 0.30 or 0.36 milligrams of human growth hormone per kilogram per week, and the fourth received daily somatropin at 0.35 milligrams per kilogram per week. The primary endpoint was annualised height velocity at week 26; secondary endpoints included the same measure at week 52 and the change in height standard deviation score, the number that places a child’s stature relative to their age and sex.
The six-month results show three weekly schedules tracking closely together. Annualised height velocity ranged from 9.23 to 10.36 centimetres per year in the lonapegsomatropin groups, against 10.86 centimetres per year in the daily hormone group. At one year, with the three weekly cohorts pooled, the rate was 9.05 centimetres per year, essentially level with the 9.04 of conventional treatment. The gain in height standard deviation score was 0.60 points on the weekly schedule and 0.67 on the daily one, a small difference. The drug was well tolerated and its safety profile was similar to that of somatropin, with no signals that forced treatment to stop.
These figures deserve the caution a phase 2 study demands. Forty-nine participants split across four arms leave few children per group, so comparisons between individual doses carry a wide margin of error; indeed, the 52-week analysis pools the three weekly cohorts, which means no single dose can be called clearly better than another. Follow-up stops at one year, long enough to measure growth velocity but far too short to know what happens to adult height, which is what families actually care about. And the design does not answer the practical question of whether the convenience of a weekly shot translates into better adherence over the long haul, even though that is precisely why these formulations are being developed.
With those caveats, the message of the trial is that lonapegsomatropin’s efficacy, safety and tolerability at one year are comparable to daily somatropin in girls with Turner syndrome, and that the three doses tested perform similarly. The authors conclude that the data support developing the drug as a once-weekly option for short stature in this syndrome, which in practice means there is still ground to cover: phase 3 studies with more participants and longer follow-up before this schedule can reach clinics. For families and for paediatric endocrinology services, the horizon is a treatment with fewer needles and, above all, with a properly pinned-down dose.
Source: Efficacy and Safety of Lonapegsomatropin in Children With Turner Syndrome: 52-Week Results From the New InsiGHTS Trial. Davis SM, Abuzzahab MJ, Tryggestad JB, Fechner PY, Gutmark-Little I, Woods K, Fadoju D, Stafford D, Nwosu BU, Iklé JM, Abdelrahman SG, Zhen X, Mao M, Komirenko AS, Shu AD, Klein KO; New InsiGHTS Investigator Group. J Clin Endocrinol Metab 2026;dgag436. DOI: 10.1210/clinem/dgag436.
Read the publication: https://doi.org/10.1210/clinem/dgag436 · PubMed 42929032
