Once-weekly growth hormone held up at two years in small-for-age children

A once-weekly growth hormone, somapacitan, kept children born small for gestational age growing through two years of treatment — and did so even in those switched over from daily injections, according to phase 3 results published in The Journal of Clinical Endocrinology & Metabolism [s1]. The appeal is practical as much as clinical: most children who moved from a daily shot to the weekly one preferred it [s1].

The problem the drug is trying to solve

Some children born small for gestational age (SGA) never catch up in height, and growth hormone can help them do so — but the standard treatment is a daily injection, a burden that falls on children and parents for years and can wear down adherence [s1]. Somapacitan is a long-acting growth hormone designed to be given once a week instead of once a day, trading six injections for one [s1]. The open question these trials address is whether weekly dosing sustains growth over the long haul, and whether switching from daily treatment loses any ground.

What the trials did

The main study, REAL8, was a randomised, multinational, open-label, active-controlled phase 3 trial with a 52-week main period and a 104-week extension, run at clinics across Europe, Asia and the Americas and registered as NCT05330325 [s2]. It randomised 142 growth-hormone-naive, prepubertal children born SGA; 141 received treatment and 139 completed 104 weeks [s1]. Children were assigned 2:1:1 to somapacitan at 0·24 mg/kg per week or to daily growth hormone at 0·035 or 0·067 mg/kg per day for the first 52 weeks; from weeks 52 to 104, everyone received the weekly somapacitan dose of 0·24 mg/kg [s1]. A smaller companion study, REAL9, was an open-label, uncontrolled phase 3 trial that enrolled 12 children or adolescents — some growth-hormone-naive, some previously treated — and gave them 0·24 mg/kg per week for 26 weeks [s1].

The primary outcome was annualised height velocity, the rate of growth in centimetres per year, with height standard deviation score (how far a child's height sits from the average for age and sex) as a secondary measure [s1].

What it found

In REAL8, mean height velocity during weeks 52 to 104 stayed above the children's baseline growth rate across all groups, at 8·5 to 8·8 cm per year — and crucially, that held true after children switched from daily growth hormone to weekly somapacitan, with no visible drop-off [s1]. Height standard deviation score continued to rise through week 104, and levels of IGF-I, the growth factor used to monitor dosing, were similar between groups [s1]. In the smaller REAL9 study, height velocity increased in the children who had never had growth hormone and was maintained in those who had been treated before [s1].

Somapacitan was well tolerated, with adverse events that were mostly mild and injection-site reactions that were infrequent [s1]. And on the question that often decides whether a treatment sticks in real life, most children switching from daily growth hormone preferred the weekly injection [s1].

Two of those measures deserve unpacking. Height velocity staying above baseline matters because untreated SGA children who have not caught up tend to grow slowly; keeping the rate elevated is how the height gap narrows over time [s1]. Height standard deviation score rising through week 104 is the cumulative version of the same thing — it tracks whether a child is moving toward the normal range for their age and sex rather than merely growing at all [s1]. That the IGF-I levels used to monitor dosing stayed similar between the weekly and daily groups is a reassurance on safety, since both too little and too much of that growth factor are undesirable [s1]. The continuity through the switch point, when every child moved onto weekly dosing, is arguably the most practically important finding: it suggests families already on daily injections could change over without losing growth.

What it means

These are open-label trials, meaning families and clinicians knew which treatment each child was receiving, and REAL9 had no control group at all — designs that can inflate subjective measures such as preference and demand cautious reading of anything beyond the hard growth numbers [s1]. The sample sizes are also small for the extension and companion study, limiting what can be said about rarer harms.

Within those limits, the finding is clear and useful: over two years, weekly somapacitan maintained growth in children born SGA with safety comparable to daily growth hormone, and children who tried both tended to prefer the weekly option [s1]. For a condition treated over years of childhood, a dosing schedule that is easier to keep up with is not a trivial advantage — provided longer follow-up confirms that final adult height, the outcome that ultimately matters, is not sacrificed for convenience.