Tansey, Michael J.Bowden, Sasigarn ArunchaiyaDauber, Andrew NahumWikiera, BeataPyrzak, BeataBossowski, Artur T.Petriczko, ElzbietaStawerska, RenataMoszczynska, ElzbietaCassorla, FernandoFeldt, Matthew M.Lunsford, Alison J.Gottschalk, Michael EverettMarin, MonicaNayak, Sunil N.Bhuvana, SunilRepaske, David RoySoyka, Leslie AnnFuqua, John S.Escobar, OscarBowlby, Deborah A.Fechner, Patricia Y.Wiltshire, EskoHarris, MarkWintergerst, Kupper A.Lafferty, Antony Richard A.Miller, Bradley S.Simm, PeterBruchey, AleksandraSmith, ChristopherKarpf, David B.McKew, John C.Thorner, Michael O.2024-03-262024-03-262023-10-05Tansey MJ, Bowden SA, Dauber AN, et al. OR21-06 Growth Response Of Oral LUM-201 In OraGrowtH210 And OraGrowtH212 Trials In Idiopathic Pediatric Growth Hormone Deficiency (iPGHD): Combined Analysis Interim Analysis Data. J Endocr Soc. 2023;7(Suppl 1):bvad114.1524. Published 2023 Oct 5. doi:10.1210/jendso/bvad114.1524https://hdl.handle.net/1805/39521Background: LUM-201 (ibutamoren), a growth hormone (GH) secretagogue receptor 1a (GHSR1a) agonist, is a potent, long-acting investigational oral GH secretagogue currently studied in three Idiopathic Pediatric GH Deficiency (iPGHD) studies. The LUM-201 predictive enrichment marker (PEM) is used to identify patients diagnosed with iPGHD (peak stimulated GH >3<10 ng/mL) who are likely to respond to LUM-201. PEM positivity is defined as a baseline insulin-like growth factor-1 (IGF-1) level >30 ng/mL and a peak GH of ≥5 ng/mL in response to a single 0.8 mg/kg dose of LUM-201. Objectives: Report the growth response analyzing the combined interim analysis (IA) data from two Phase 2 trials studying LUM-201 at two different doses (1.6 mg/kg/day or 3.2 mg/kg/day). Methods: IA data from both studies were combined and analyzed for calculated annualized height velocity (AHV). Baseline demographics were analyzed for the two combined cohorts. Results: After 6 months of treatment with LUM-201, the calculated AHV (mean ±SD ) was 8.1±1.9 cm/year in the 1.6 mg/kg/day group and 8.0±1.5 cm/year in the 3.2 mg/kg/day group (N=15 in both groups). After 9 months of treatment, the calculated AHV was 7.8±1.7 cm/year in the 1.6 mg/kg/day group and 7.3±1.7 cm/year in the 3.2 mg/kg/day group (N=10 in both groups). After 12 months of treatment, the calculated AHV was 7.8±1.7 cm/year in the 1.6 mg/kg/day group and 7.4 ±1.2 cm/year in the 3.2 mg/kg/day group (N=6 in both groups). LUM-201 was well tolerated; no safety concerns were identified across the dose range in adverse events (AE) data, laboratory values, and ECG values. Conclusions: As the growth velocity was comparable for the two doses of oral LUM-201, this analysis of the combined IA data appears to strongly support 1.6 mg/kg/day as the optimal dose for the Phase 3 trial, as doubling the dose appeared to offer no meaningful improvement in efficacy. Final determination will await final full data set analysis of both studies.en-USAttribution-NonCommercial-NoDerivatives 4.0 InternationalIbutamorenLUM-201Growth hormone (GH) secretagogue receptor 1a (GHSR1a)Abstract