Summary: In treatment-naive children with growth hormone deficiency (n=200), once-weekly somapacitan sustained growth over three years, with mean height SD score reaching -0.95 in the continuous-somapacitan arm and -1.08 in the arm switched from daily GH at one year, both approaching the mean mid-parental HSDS of -0.74. This open-label phase 3 extension was descriptive and showed outcomes similar between arms rather than superiority over daily growth hormone.
PICO Summary
| Element | Detail |
|---|---|
| Population | 200 treatment-naive children with growth hormone deficiency; randomized, multinational, open-label, active-controlled parallel-group phase 3 trial with a 52-week main phase plus 3-year safety extension (REAL4, NCT03811535); 188 completed 3 years. |
| Intervention | Continuous once-weekly somapacitan 0.16 mg/kg/week (“soma/soma” arm) for 3 years; 2:1 randomization favoured this arm. |
| Comparison | Daily GH (Norditropin 0.034 mg/kg/day) for the first year, then switched to once-weekly somapacitan 0.16 mg/kg/week (“switch” arm). |
| Outcome | At week 156, mean (SD) height velocity over weeks 104-156 was 7.4 (1.5) cm/year (soma/soma) versus 7.8 (1.4) cm/year (switch). Mean (SD) HSDS was -0.95 (0.98) versus -1.08 (0.93), both approaching mid-parental HSDS of -0.74. Mean total IGF-I SDS in year 3 was within the normal range (-2.0 to +2.0) and similar between arms, as were bioactive IGF-I measures. Outcomes were reported as similar between arms; no between-arm hypothesis test, 95% CI, p-value, or ARR/NNT was presented for the 3-year efficacy endpoints. Tolerability was good with low rates of injection-site reactions. |
Expert Commentary
These 3-year REAL4 extension data are reassuring but should be read as descriptive rather than as proof that weekly somapacitan is superior to daily growth hormone. Sustained height velocity and a mean HSDS approaching the mid-parental target were observed in both the continuously treated children and those switched after one year, and IGF-I exposure stayed within the normal range. What is not provided for the 3-year endpoints is any between-arm statistical comparison: no confidence intervals, p-values, or non-inferiority margins are reported here, so the headline is consistency over time, not a demonstrated efficacy advantage. The pivotal 52-week phase was designed for non-inferiority, and these results are best framed as supporting durable growth and a smooth transition from daily to weekly dosing. Two important caveats temper enthusiasm. The trial is open-label, which can bias subjective assessments and adherence, and it was sponsored by the manufacturer of both study drugs, with company-affiliated authors. Can I use this with my patients? Cautiously yes, for children with confirmed growth hormone deficiency already considered for replacement, where a weekly injection may ease treatment burden, and for those tolerating daily GH who wish to switch. Longer comparative and real-world data on final adult height and long-term safety remain desirable before weekly dosing is treated as fully interchangeable.
References
Miller BS, Blair JC, Rasmussen MH, Frystyk J, Lemminger AK, Maniatis A, et al. Efficacy, safety, and insulin-like growth factor I of weekly somapacitan in children with growth hormone deficiency: 3-year results from REAL4. Eur J Endocrinol. 2025;192(5):651-661. doi:10.1093/ejendo/lvaf096