SUN-658 Ibutamoren Mesylate, an Oral Growth Hormone (GH) Secretagogue, Modifies Body Composition in Healthy Older Adults by Increasing Both the Amount and the Pattern of Endogenous GH Secretion

Abstract Disclosure: A. Roslan: Lumos Pharma, Inc.. R. Nass: None. P. Veldhuis: None. J. McKew: Lumos Pharma, Inc. P. Pitukcheewanont: Lumos Pharma, Inc. E. Brincks: Lumos Pharma, Inc. P.E. Clayton: Lumos Pharma, Inc. M. Thorner: Lumos Pharma, Inc. A. Stevens: Lumos Pharma, Inc.. Background: Ibutamoren (IB, LUM-201), an investigational oral GH secretagogue, increased pulsatile GH secretion and fat-free mass (FFM) in healthy older adults to levels seen in young adults in a double-blind, placebo-controlled trial to assess its potential as treatment for sarcopenia (Nass et al Ann Intern Med. 2008). In children with moderate GH deficiency the growth response to IB is related to both the amount and pattern of GH secretion; the latter was identified using functional principal component analysis (FPCA) to define the timing and extent of the dominant variation in 12hr day-time GH profiles (FC15.2, ESPE 2024). This study uses FPCA to assess the effect of the first 6 months of treatment with IB in adults on the relationship between change in FFM and patterns of GH secretion in 12hr day-time and 24hr GH profiles. Methods: 65 healthy adults (23 men, 25 women on HRT, 17 not on HRT) ranging from 60-81 years old received oral IB 25 mg (n=43) or placebo (n=22) once daily for 6m. FFM (kg) was measured by DXA and samples for GH were drawn every 10mins for 24hr at baseline and 6m in the IB and placebo groups. GH secretory dynamics were assessed using deconvolution; analysis was undertaken on the 12hr day-time data and the full 24hr GH secretion profile (µg/L/min). FPCA defines the GH profile variation as Eigen Functions, with the first EF [EF1] used in this analysis. L2 Norm (the Euclidean distance between the EF1 profile at baseline and 6m) was used to define differences in IB and placebo groups. For the FPCA, the change in FFM over 6m in IB and placebo groups were both stratified into tertiles and the total GH production and EF1 profiles in each tertile were compared within and between groups. Significance was evaluated by Kruskal-Wallis and Wilcoxon tests. Results: In the whole cohort over 6m, total GH production increased in the IB-treated group (median change +23, range -21 to 92 µg/L over 24hr) but not on placebo (+2.3, -56 to +162), p<0.0001. FFM increased in the IB group (median +1, range -2.7 to +4.1kg) but not on placebo (-0.1, -3.7 to +2.9kg), p<0.001. Across the FFM tertiles in IB and placebo groups, total GH production over 24hr was not different (with the placebo group having lower levels, as expected), suggesting that amount of GH alone was not accounting for the range of FFM changes. However across FFM tertiles the differences in the EF1 profiles over 6m derived from the 12hr day-time and 24hr GH profiles for IB and for placebo were significant (both p<0.0001). Additionally within each FFM tertile the EF1 profiles were different between IB and placebo groups (all p<0.0001). Conclusions: This analysis indicates both the amount and the variation in GH secretion in healthy older adults treated with IB influences changes in body composition, in both for the 12hr day-time GH secretion and for the full 24hr profile. These effects of Ibutamoren on physiological GH secretion reinforce the importance of pulse profiles to GH action. Presentation: Sunday, July 13, 2025