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Endocrine Abstracts (2024) 99 P120 | DOI: 10.1530/endoabs.99.P120

ECE2024 Poster Presentations Pituitary and Neuroendocrinology (120 abstracts)

Approaching the reality of restoring GH secretion and growth with the investigative oral growth hormone secretagogue (GHS) LUM-201 in moderate pediatric growth hormone deficiency (PGHD)

Peter Clayton 1 , Fernando Cassorla 2 , OraGrowtH210 Trial Group 3 , OraGrowtH212 Trial Group 3 , Michael Johnson 4 , Aleksandra Bruchey 3 , Christopher Smith 3 , Erik Brincks 3 , Pisit ’ Duke’ Pitukcheewanot 3 , John McKew 3 & Michael Thorner 3


1University of Manchester, Division of Developmental Biology & Medicine; Paediatric Endocrinology, Manchester, United Kingdom; 2University of Chile, Institute of Maternal and Child Research, Santiago, Chile; 3Lumos Pharma, Inc., Austin, TX, United States; 4University of VA Health System, Keswick, VA, United States


Over 40 years ago, the first enkephalin analogs that stimulated growth hormone (GH) release were synthesized in 1984, leading to the development of GHRP-6. In 1995, Merck developed a potent non-peptide orally active long-acting growth hormone GHS, ibutamoren, and cloned the GHS receptor in 1996, which led to ghrelin being identified as its natural ligand in 1999. These discoveries uncovered a new physiological pathway for GH regulation linking the GI tract and the hypothalamic-pituitary axis (HPA). In 1998, the first oral ibutamoren (now known as LUM-201) clinical trial in PGHD included pre-pubertal children with a broad spectrum of PGHD, resulting in positive growth responses coming from those with an intact HPA. Later, it was understood the best candidates for this investigative oral treatment were pre-pubertal children (those with standard stimulation testing peak GH between ≥3 <10 ng/ml) that respond positively to the LUM-201 Predictive Enrichment Marker (PEM) test. PEM+ responders have basal serum IGF-1 >30 ng/ml and a peak serum GH ≥5 ng/ml after administering a single dose of 0.8 mg/kg LUM-201. Oral once-daily LUM-201 has been studied in two phase 2 trials in PEM+ PGHD focusing on safety and effectiveness. The OraGrowtH212 trial has evaluated GH pulse profiles at baseline and after 6 months of LUM-201 at 1.6 and 3.2 mg/kg/day, while the OraGrowtH210 trial has investigated dose responses using 0.8, 1.6, and 3.2 mg/kg/d vs rhGH comparator arm. The OraGrowtH212 trial demonstrated a 62% increase in GH secretion and an 80% increase in IGF-1 concentration after 6 months of LUM-201, enhancing annualized height velocity (AHV) by 60%, which remained steady at 12 months. In the OraGrowtH210 trial, the 1.6 mg/kg/d dose achieved the highest AHV over 6 months (8.2 cm/yr), maintained at 12 months (8.0 cm/yr), comparable to historical responses in moderate PGHD and within the targeted 2 cm/yr margin of the rhGH comparator arm. Notably, LUM-201 achieved the reported growth rates with GH secretion at approximately one-fifth of the amount absorbed from daily rhGH injection. Both studies reported a favorable investigational safety profile. Oral LUM-201 allows the restoration of normal pulsatile endogenous GH secretion to support similar growth to that achieved with daily pharmacological rhGH while maintaining normal feedback mechanisms. This innovative approach to treating PGHD will remove the burden of frequent injections with an oral therapy that achieves physiological GH profiles and therefore meets the core objectives of all endocrine therapies, namely to restore normal hormonal homeostasis.

Volume 99

26th European Congress of Endocrinology

Stockholm, Sweden
11 May 2024 - 14 May 2024

European Society of Endocrinology 

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