ESPE Yearbook of Paediatric Endocrinology

J Clin Endocrinol Metab 2025 Mar 17;110(4):e1232-e1240. PMID: 39672599. doi: 10.1210/clinem/dgae834

Brief Summary: This consensus statement, developed by an international workgroup of 11 pediatric endocrinology experts from 10 countries, provides practical guidance on the use of long-acting growth hormone (LAGH) therapy for children with GHD. The panel included clinicians and researchers with extensive expertise in daily GH and LAGH therapy, as well as active involvement in related clinical trials and publications.

Once-weekly LAGH formulations (lonapegsomatropin, somapacitan, and somatrogon) have been approved following pivotal phase 3 studies. Their main advantage over daily GH is reduced injection frequency, which may improve adherence and quality of life, particularly as suboptimal adherence to daily GH is common and negatively affects linear growth. Surveys indicate that patients and caregivers strongly prefer LAGH due to lower treatment burden.

Phase 3 trials have shown that LAGHs are noninferior to daily GH in promoting height gain in prepubertal children with GHD. The safety profiles of LAGHs are comparable to daily GH, with no new safety concerns observed during follow-up periods up to five years. Notably, somatrogon was associated with more frequent injection site reactions and pain.

Most children with GHD are eligible for LAGH. Particular benefit may be expected in groups at higher risk of poor adherence—such as adolescents, children with needle phobia or neurodiversity, those living in multiple households, or those who travel frequently.

Dosing and monitoring:

• Dose adjustments are weight-based, similar to daily GH.

• IGF1 levels remain central to treatment monitoring. Samples should be collected ~4 days after somapacitan/somatrogon administration or ~4.5 days after lonapegsomatropin to approximate mean IGF1 exposure.

• The target is an average IGF1 SDS within the normal range (−2 to +2, ideally near 0 SDS).

• Direct milligram-to-milligram comparisons between LAGH molecules are inappropriate because of differing pharmacokinetic and pharmacodynamic properties.

• LAGH therapy offers a more flexible window for delayed dosing (±2–3 days) compared to daily GH.

Knowledge gaps and research needs: Significant gaps remain in long-term, real-world evidence on adherence, safety, and efficacy, including impacts on adult height, body composition, and cardiometabolic health. Additional data are especially needed for patient subgroups underrepresented in trials: cancer and intracranial tumor survivors, very young children (due to hypoglycemia risk), and those with non-GHD indications such as SGA, ISS, Turner, Noonan, SHOX deficiency, and chronic kidney disease.

Conclusion: The consensus underscores the importance of shared decision-making between clinicians, patients, and caregivers when considering LAGH. Ongoing real-world data collection, through registries like GloBE-Reg, will be critical to refine clinical practice and optimize outcomes.

References: 1. Growth Hormone Research Society. Consensus guidelines for the diagnosis and treatment of growth hormone (GH) deficiency in childhood and adolescence: summary statement of the GH Research Society. J Clin Endocrinol Metab. 2000;85(11):3990-3993.2. Grimberg A, DiVall SA, Polychronakos C, et al. Guidelines for growth hormone and insulin-like growth factor-I treatment in children and adolescents: growth hormone deficiency, idiopathic short stature, and primary insulin-like growth factor-I deficiency. Horm Res Paediatr. 2016;86(6):361-397.3. Cutfield WS, Derraik JG, Gunn AJ, et al. Non-compliance with growth hormone treatment in children is common and impairs linear growth. PLoS One. 2011;6(1):e16223.4. Miller BS, Blair JC, Rasmussen MH, et al. Weekly somapacitan is effective and well tolerated in children with GH deficiency: the randomized phase 3 REAL4 trial. J Clin Endocrinol Metab. 2022;107(12):3378-3388.5. GloBE-Reg. 2024. REAL10 Study. Accessed April 2024.