Summary: In adults with growth hormone deficiency, once-weekly lonapegsomatropin reduced trunk fat percentage more than placebo at 38 weeks: least-squares mean difference -2.04 percentage points (P<0.001). Body-composition benefits were demonstrated, but the trial did not establish equivalence or superiority to daily somatropin.
PICO Summary
| Element | Detail |
|---|---|
| Population | 259 adults with growth hormone deficiency were randomised and dosed across 116 centres in North America, Europe and Asia-Pacific. The trial included three treatment groups; five additional randomised participants were not dosed and were excluded from the intention-to-treat population. |
| Intervention | Once-weekly subcutaneous lonapegsomatropin, individually titrated during the 38-week study; 89 participants dosed. |
| Comparator | Once-weekly placebo in the double-blind primary comparison (84 dosed). A third group received open-label daily somatropin (86 dosed) as an active reference; no formal efficacy comparisons between lonapegsomatropin and daily somatropin were conducted. |
| Outcomes | At week 38, trunk fat percentage changed by -1.68 percentage points with lonapegsomatropin versus +0.37 with placebo; adjusted difference -2.04 percentage points (95% CI -2.94 to -1.14; full-text P<0.0001). Secondary differences versus placebo: total lean mass +1.70 kg (95% CI 0.95 to 2.46; P<0.0001) and trunk fat mass -0.70 kg (95% CI -1.20 to -0.21; full-text P=0.005). Serious adverse events occurred in 4/89, 1/84 and 6/86 participants on lonapegsomatropin, placebo and daily somatropin respectively. One drug-related serious event occurred with each active treatment: hyponatraemia with lonapegsomatropin and facial/peripheral oedema with somatropin. No deaths occurred. Similar descriptive safety does not establish equivalence; clinical event reduction was not tested. |
| Study Design | foresiGHt: multicentre, randomised, parallel-arm, 38-week trial with a double-blind placebo comparison and open-label active-control arm. Allocation 1:1:1. Primary outcome: change in trunk fat percentage. Funded by Ascendis Pharma. ClinicalTrials.gov NCT04615273. |
Expert Commentary
I interpret foresiGHt as a positive placebo-controlled replacement-therapy trial with a potentially useful reduction in injection burden. Improved trunk fat and lean mass provide coherent evidence of biological efficacy in adults with established growth hormone deficiency. The distinction between the two comparators is crucial: placebo was double-blind, whereas daily somatropin was open-label and no formal efficacy comparison with it was conducted. Similar-looking results therefore do not establish equivalence, non-inferiority or superiority to daily treatment. The main limitation for clinical decision-making is that body composition is not the same as improved function, quality of life or long-term cardiovascular health. Thirty-eight weeks also provides limited reassurance about uncommon or delayed adverse effects. Ascendis Pharma funding and manufacturer-affiliated authorship should be acknowledged. Can I use this with my patients? The findings can support a specialist discussion about weekly replacement for appropriately diagnosed adults where locally authorised, but not growth hormone use for uncomplicated obesity, ageing or nonspecific fatigue. Dosing, interpretation of IGF-I and ongoing monitoring should follow the product-specific requirements rather than being inferred from an abbreviated trial summary. I would want longer comparative follow-up, patient-reported treatment burden and robust clinical safety data to establish whether the convenience translates into sustained benefit outside the trial.
References
Biller BMK, Gilis-Januszewska A, Doknic M, et al. Efficacy and Safety of Once-Weekly Lonapegsomatropin in Adults With Growth Hormone Deficiency: foresiGHt Trial Results. J Clin Endocrinol Metab. 2026;111(6):1640-1650. doi:10.1210/clinem/dgaf680. PMID: 41420532.
