THU195 6-Month Subcutaneous Leuprolide Acetate Achieved And Maintained Hormonal And Clinical Suppression In All Weight Groups Of Children With Central Precocious Puberty

Abstract

Disclosure: B.S. Miller: Consulting Fee; Self; Abbvie, Ascendis Pharma, Bristol Myers Squibb, BioMarin, Endo Pharmaceuticals, EMD Serono, Novo Nordisk, Pfizer, Tolmar Pharmaceuticals. Research Investigator; Self; Alexion, Abbvie, Aeterna Zentaris, Amicus, Lumos Pharma, Lysogene, Novo Nordisk, OPKO Health, Pfizer, Prevail Therapeutics, Sangamo Therapeutics. D. Boldt-Houle: Employee; Self; Tolmar Pharmaceuticals, Inc. S.N. Atkinson: Employee; Self; Tolmar Pharmaceuticals, Inc.

Background: Childhood obesity is associated with an increased risk of central precocious puberty (CPP). ¹ Thus, data on whether weight status affects the treatment of children with CPP would be valuable to help clinicians ensure correct management. We present secondary analyses of hormone and height velocity (HV) data from the pivotal trial of the first small-volume, long-acting, subcutaneously administered gonadotropin-releasing hormone agonists (GnRHa) for CPP, with the goal of assessing if the study drug adequately suppresses hormones in overweight and obese children. Methods: 62 children with treatment-naïve CPP received 2 doses of 45 mg subcutaneous leuprolide acetate at 24-week intervals over the 48-week study period. The BMI percentile for children was calculated based on the Center for Disease Control growth charts, accounting for height, weight, age, and gender. Luteinizing hormone (LH) concentrations were assessed using a validated central Cobas ECLIA assay with a lower limit of detection of 0.100 IU/L. Estradiol (E2) concentrations were assessed using liquid chromatography-tandem mass spectrometry/mass spectrometry (LC-MS/MS) with a lower limit of detection of 10 pg/mL. HV was calculated as the change in height between visits/((number of weeks between visits)/52). Results: Mean GnRH-stimulated LH concentrations at screening, week 24, and week 48 were 24.5, 2.1, and 2.5 IU/L in non-overweight children, 10.5, 3.2, and 2.2 IU/L in overweight children, and 31.5, 4.8, and 1.9 IU/L in obese children, respectively. In these same groups, mean E2 concentrations at screening, week 24, and week 48 were 28.2, 10.5, and 10.3 pg/mL in non-overweight children, 17.8, 10.4, and 10.4 pg/mL in overweight children, and 25.9, 11.0, and 11.1 pg/mL in obese children, respectively. Mean HV at week 4, week 24, and week 48 was 10.2, 5.6, and 5.7 cm/year in non-overweight children, 7.7, 5.5, and 6.2 cm/year in overweight children, and 8.2, 4.9, and 6.6 cm/year in obese children, respectively. Conclusions: Subcutaneous leuprolide acetate effectively treated all overweight children without any requirement for weight-based dosing. This is consistent with results from previous studies of GnRHa efficacy in obese and normal-weight children with CPP. ² Clinicians should consider providing counseling and interventions that support healthy diets and lifestyles to children with above-normal BMI and their caregivers. References Cited 1.Liu G, Guo J, Zhang X, Lu Y, Miao J, Xue H. Obesity is a risk factor for central precocious puberty: a case-control study. BMC Pediatr. 2021;21(1):509.2. Chen M, Eugster EA. Central precocious puberty: update on diagnosis and treatment. Paediatr Drugs. 2015;17(4):273-281.

Presentation: Thursday, June 15, 2023