ODP397 Small-volume, Subcutaneous, 6-month Leuprolide Acetate Effectively Reduces Growth Velocity to Prepubertal Levels in Children with Central Precocious Puberty

Abstract

Introduction

Clinical signs of puberty, growth rate, rate of bone maturation, luteinizing hormone concentrations and estimates of change in predicted adult height are the common variables for assessing efficacy of central precocious puberty (CPP) therapies. (1, 2) All clinical and laboratory parameters are essential when interpreting treatment response. (3) Preservation of adult height potential is an important goal of CPP treatment and accelerated growth velocity can contribute to reduced adult height. (4) We present secondary analyses of growth velocity data from the pivotal trial of the first small-volume, long-acting, subcutaneously administered GnRH agonist for central precocious puberty (CPP), approved in 2020. (5) Methods: 62 children (60 girls, 2 boys) with treatment-naïve CPP received 2 doses of 45 mg subcutaneous leuprolide acetate at 24-week intervals. We measured standing height with a calibrated stadiometer at Baseline and Weeks 4, 12, 20, 24, 36, 44, and 48. Growth velocity (cm/year) was calculated as a change in height (cm) between visits/((number of weeks between visits)/52).

Results

Mean growth velocity decreased throughout treatment from 10.4 cm/year for the time period from screening to baseline to 6. 0 cm/year for Week 34 to 48. The proportion of children who achieved growth velocity 4-6 cm/year increased 2.5-fold from baseline (10%) to Week 48 (25%).

Conclusions

Subcutaneous leuprolide acetate effectively decreased growth velocity to prepubertal rates in children with CPP. Mean growth velocity from Week 24 to 48 was similar to what is seen in children of the same age without CPP (5.8-6.1 cm/year, depending on sex and race). (6) These data indicate that subcutaneous leuprolide acetate may increase adult height and improve the likelihood of achieving genetic target height range. References Cited 1. Klein KO, et al. Phase 3 trial of a small-volume subcutaneous 6-month duration leuprolide acetate treatment for central precocious puberty. JCEM. 2020. 2. Lee HS, et al. Increased final adult height by gonadotropin-releasing hormone agonist in girls with idiopathic central precocious puberty. PLoS One. 2018. 3. Klein KO, Lee PA. Gonadotropin-releasing hormone (GnRHa) therapy for central precocious puberty (CPP): Review of nuances in assessment of height, hormonal suppression, psychosocial issues, and weight gain, with patient examples. PER. 4. Chen M, Eugster EA. Central Precocious Puberty: Update on Diagnosis and Treatment. Paediatr Drugs. 2015. 5. FENSOLVI® (leuprolide acetate) for injectable suspension, for subcutaneous use [prescribing information]. 2020. 6. Kelly A, et al. Age-based reference ranges for annual height velocity in US children. JCEM. 2014.

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