ESPE2023 Free Communications Late Breaking (6 abstracts)
Deconvolution Analysis: GH secretagogue (LUM-201) enhances growth in individuals with moderate idiopathic Pediatric Growth Hormone Deficiency (iPGHD) by enhancing endogenous GH secretion and increasing IGF-1
Fernando Cassorla, MD1, Rossana Román, MD1, Michael Linn Johnson, PhD2, Alejandra Avila, RN1, German Iñiguez, MD1, Ingrid Baier, MD1, Daniela Said, RN1, Aleksandra Bruchey, PhD3, Christopher Smith, MS3, Erik L. Brinks, PhD3, John C. McKew, PhD3, David B. Karpf, MD3, Michael O. Thorner, MD, MBBS, DSc3
1Institute of Maternal and Child Research, University of Chile, Santiago, Chile. 2University of Virginia-Emeritus, Charlottesville, USA. 3Lumos Pharma, Inc., Austin, USA
An oral GH secretagogue (GHS), LUM-201, stimulates GHSR-1a receptor to enhance endogenous GH pulsatile release. In moderate iPGHD, pulses of GH are found but at reduced levels, resulting in decreased IGF-1 and poor growth. The impact of LUM-201 on GH profiles during treatment of such children has not been reported.
Objective: To characterize GH profiles, defined by deconvolution analysis, based on GH concentration in a time series and its simultaneous clearance, at baseline and after 6 months of therapy with daily oral LUM-201 to illustrate how it affects annualized height velocity (AHV), serum IGF-1 and IGFBP3 in individuals with moderate iPGHD.
Patients & Methods: 15 prepubertal, naive iPGHD subjects were screened with a predictive enrichment marker (PEM) test to assess their acute response to oral LUM-201 (0.8mg/kg), with a positive test having a peak GH >5 ng/ml with a basal IGF-1 >30 ng/ml. At baseline, subjects (10M:5F) were (mean ± SD) aged 7.9±1.4 years, with IGF-1 SDS -0.82±0.9, and peak GH 7.2±2.2 ng/mL (clonidine stimulation), consistent with moderate iPGHD. Deconvolution was performed on serum GH measured every 10 minutes (0800 h to 2000 h). Patients were randomized to receive 1.6 mg/kg/day or 3.2 mg/kg/day of oral LUM-201. GH responses to the PEM test (P=0.9) and the first treatment doses were not different between the groups (34.8±6.6ng/ml for 1.6mg/kg and 38.2±11.2 ng/ml for 3.2mg/kg, P=0.7). The groups were therefore combined for this analysis.
Results: At 6 months GH & IGF parameters, and AHV increased 1.2-2.4 fold: See Table for means (SD).
| Baseline | 6 Month | t test, p value | |
| GH total* | 1.45 (0.89) | 2.32 (1.25) | 0.013 |
| GH pulsatile* | 1.28 (0.83) | 1.93 (1.17) | 0.035 |
| GH basal * | 0.17 (0.11) | 0.40 (0.28) | 0.008 |
| AHV (cm/year) | 4.7 (1.3) | 7.6 (1.1) | < 0.00001 |
| IGF-1 (ng/mL) | 115.5 (46.6) | 205.4 (63.9) | 0.0004 |
| IGFBP3 (nmol/L) | 139.3 (32.6) | 169.0 (30.1) | 0.0004 |
| IGF-1:IGFBP3 | 0.108 (0.031) | 0.157 (0.050) | 0.0044 |
| *daytime secretion μg/kg body weight per 12hr | |||
Conclusions: LUM-201 generated the expected AHV in this iPGHD cohort. LUM-201 enhanced pulsatile GH secretion to similar levels observed in normal growing children, estimated at ~3.5?g/kg/12h (Albertsson-Wikland et al JCEM 1994); restoring physiological pulsatile GH secretion and IGF-1 were sufficient to support normal growth. LUM-201 in the treatment of moderate iPGHD has the advantages of being taken orally, enhancing endogenous pulsatile GH secretion, and therefore maintaining normal feedback mechanisms, to restore normal growth
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