medwireNews: An oral growth hormone secretagogue receptor (GHSR1a) agonist produces larger GH responses than standard stimulation tests in children with growth hormone deficiency (GHD), study findings suggest.
“Stimulation of the GHSR1a evokes a number of responses including increased secretion of GHRH [growth hormone-releasing hormone] and decreased secretion of somatostatin from the hypothalamus”, explain study authors George Bright and Michael Thorner, both from Lumos Pharma Inc in Austin, Texas, USA.
This leads to “potentiation of the GHRH stimulus on pituitary somatotrophs and direct stimulatory effects on GH release on the somatotrophs”, they add.
For this analysis, the team looked at maximal GH responses to the GHSR1a agonist LUM-201 (also known as ibutamoren mesylate), given at an oral dose of 0.8 mg/kg, in comparison to two standard stimuli in 40 boys and 28 girls who participated in a GHD clinical trial.
The participants were prepubertal but at least 4 years old, had a median height standard deviation score of –3.3, a 6-month height velocity below the 10th centile for their age and sex, and a bone age delay of at least 1 year.
The children had a peak GH response to two standard stimuli (eg, glucagon, clonidine, insulin) of less than 10.0 ng/mL, with a median of 5.4 ng/mL.
“It should be mentioned that GH stimulation test results in the range of 5–10 ng/mL are not considered indicative of GHD by all pediatric endocrinologists”, write the researchers in Hormone Research in Paediatrics.
The range of responses to standard stimulants was 0.8 to 10.0 ng/mL, whereas the responses to LUM-201 were significantly higher, ranging from 1.9 to 103 ng/mL, with a median of 15.0 ng/mL. Just three children had a higher GH peak in response to standard test than to LUM-201.
Stepwise multiple regression analysis identified baseline insulin-like growth factor (IGF)-1 level and response to standard GH stimulation tests as together explaining 73% of the variation in response to LUM-201. The higher these two factors were, the higher was the children’s response to LUM-201.
“These data suggest a different mechanism of action on GH release for LUM-201 than for the standard diagnostic stimuli”, say Bright and Thorner, noting that standard stimuli are not thought to act via GHSR1a.
They suggest that the mode of action of LUM-201 may allow more reproducible GH-stimulation results than achieved with standard tests, and say that this and the ability of LUM-201 to produce a higher GH response than standard stimuli are being assessed in an ongoing study.
And they say that this ongoing trial “is also a Phase 2 study to determine if LUM-201 and daily [recombinant human] GH give comparable 6-month height velocity responses in prepubertal children from the GHD spectrum selected by higher baseline IGF-1, higher GH responses to standard GH stimuli, and peak GH responses to single-dose LUM-201.”
By Eleanor McDermid
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Horm Res Paediatr 2022; doi:10.1159/000524244