Real world data on rhIGF-1 therapy in children with severe primary IGF-I deficiency - The European experience.

The Growth Hormone - Insulin-like Growh Factor - axis promotes linear growth in children and adolescents and accounts for approximately 1/3 of adult height. In Primary IGF-I deficiency (PIGFD) insensitivity to the actions of GH results in short stature. The most severe phenotype in children with genetic defects in the GH receptor gene is known as Laron Syndrome with height SDS of -6 to -12 in childhood and an adult height of 120-130 cm. Treatment with recombinant human (rh) IGF-1 is approved to promote linear growth in children with severe PIGFD and the EMA approval required that data on children on therapy and up to 5 years post-treatment is collected in the Global Increlex Growth Forum Database (IGFD) registry. In this review, the findings in five publications on rhIGF-1 therapy in children with SPIGFD based on data from the Global IGFD registry are discussed and compared with previous publications on cohorts of patients with severe PIGFD including children with Laron Syndrome. The registry started inclusion of patients in 2008 from 10 European countries (EU IGFD Registry) and have continued collecting data from eight European countries and the US since 2021 (Global IGFD registry). At data cut-off (03 April 2025), there were 346 patients in the registry database including patients with a large variation of phenotypes from Laron Syndrome to a less severe phenotype. The findings include real-world data on effectiveness assessing short- and long-term height gain as well as near adult height, pubertal development and growth dynamics and safety assessing hypoglycemic events, which is the most frequent targeted adverse event. Real-world data from the Global IGFD registry confirms previous data on rhIGF-1 therapy and demonstrates that short and long-term height improves in a majority of children with SPIGFD with similar height improvements compared to children with Laron Syndrome. The registry data points to baseline characteristics including age at treatment initiation that predicts response to therapy. Hypoglycemia is the most common adverse event and hypoglycemia prior to start of therapy or a diagnosis of Laron Syndrome increases the risk. However, very few events over a course of therapy are reported on an individual basis.