Abstract

Context

We hypothesize, based on the degree of residual hypothalamic-pituitary function, that some, but not all, children with growth hormone deficiency (GHD) may have beneficial growth responses to the orally administered growth hormone (GH) secretagogue LUM-201.

Objective

To determine if pretreatment testing can identify predictive enrichment markers (PEM) for subjects with adequate residual function who are responsive to LUM-201.

Methods

We performed an analysis of a completed, randomized, placebo-controlled trial of LUM-201, a GH secretagogue receptor agonist, in which all randomized subjects had pretreatment testing.

This international multicenter study conducted in pediatric endocrinology clinics included 68 naïve-to-treatment, prepubertal children with established diagnoses of GHD. Outcome measures included the sensitivity, specificity, and predictive accuracy of potential markers to predict 6-month growth responses to oral LUM-201 and daily rhGH.

Results

Two PEM were identified for use in defining PEM-positive status: (1) baseline insulin-like growth factor I (IGF-I) concentration >30 ng/mL and (2) peak GH response of ≥5 ng/mL upon administration of single-dose LUM-201. PEM-positive status enriches a population for better growth responses to LUM-201. PEM-negative status enriches a population for better growth responses to rhGH.

Conclusion

Combined, the peak GH response to single-dose LUM-201 and the baseline IGF-I concentration are effective PEMs for 6-month growth responses to LUM-201 and rhGH in prepubertal children with GHD.

Details

Title
Development of a Predictive Enrichment Marker for the Oral GH Secretagogue LUM-201 in Pediatric Growth Hormone Deficiency
Author
Bright, George M 1 ; Do, Minh-Ha T 1 ; McKew, John C 1 ; Blum, Werner F 2 ; Thorner, Michael O 1 

 Lumos Pharma, Inc ., 4200 Marathon Blvd., Suite 200, Austin, Texas 78756, USA 
 Center of Child and Adolescent Medicine, Justus-Liebig University, 35390 Giessen, Germany 
Publication year
2021
Publication date
Jun 2021
Publisher
Oxford University Press
e-ISSN
24721972
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
3170635765
Copyright
© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. This work is published under http://creativecommons.org/licenses/by-nc-nd/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.