5162 Oral LUM-201 Restores Pulsatile Growth Hormone Secretion and Growth Response in Moderate Pediatric Growth Hormone Deficiency (PGHD): Key Discoveries from Phase 2 of OraGrowtH212 Trial

Abstract

Abstract Disclosure: F. Cassorla: Consulting Fee; Self; Lumos Pharma, Inc. Research Investigator; Self; Lumos Pharma, Inc. R. Roman: Research Investigator; Self; Lumos Pharma, Inc. M.L. Johnson: Consulting Fee; Self; Lumos Pharma, Inc. A. Avila: Research Investigator; Self; Lumos Pharma, Inc. G. Iñiguez: Research Investigator; Self; Lumos Pharma, Inc. I. Baier: Research Investigator; Self; Lumos Pharma, Inc. D. Said: Research Investigator; Self; Lumos Pharma, Inc. A. Bruchey: Employee; Self; Lumos Pharma, Inc.. Stock Owner; Self; Lumos Pharma, Inc. C. Smith: Employee; Self; Lumos Pharma, Inc.. Stock Owner; Self; Lumos Pharma, Inc. E. Brincks: Employee; Self; Lumos Pharma. Stock Owner; Self; Lumos Pharma, Inc. J. McKew: Employee; Self; Lumos Pharma. Stock Owner; Self; Lumos Pharma. M.O. Thorner: Consulting Fee; Self; Lumos Pharma, Inc.. Stock Owner; Self; Lumos Pharma, Ammonett Pharma LLC. P. Pitukcheewanont: Employee; Self; Lumos Pharma. Stock Owner; Self; Lumos Pharma. Objectives: The primary objective was to examine the pharmacokinetic/pharmacodynamic (PK/PD) aspects of oral LUM-201 at doses of 1.6 and 3.2 mg/kg/d with moderate PGHD, involving frequent GH sampling for 12 hours post-administration. Using deconvolutional analysis, the study compared the GH secretion patterns before & after 6 months (m) daily administration of LUM-201. LUM-201, an investigational agonist of the growth hormone (GH) Secretagogue Receptor 1a (GHSR1a), was employed as part of a predictive enrichment marker (PEM) test to identify moderate PGHD subjects likely to respond, based on baseline insulin-like growth factor-1 (IGF-1) level >30 ng/mL & a peak GH of ≥5 ng/mL post a single 0.8 mg/kg dose of LUM-201. Methods: The OraGrowtH212 Trial, conducted at Santiago, Chile, monitors subjects until they approach their near final height. The current report focuses on data analysis at 6 and 12m, with ongoing subject follow-ups extending to 24m. This trial randomized 22 PEM+ moderate PGHD subjects into two LUM-201 dosage groups: 1.6 or 3.2 mg/kg/d. To assess GH secretion, each child was sampled every 10 min from 0800-2000h at baseline & 6m. Safety was assessed throughout the study and growth evaluated at 6 & 12m intervals. Results: At start of the study, basal GH secretion in the LUM-201 1.6mg/kg/d group (all values expressed as mean ± SD µg/kg body weight) was 0.19 ±0.09, pulsatile GH was 1.17 ± 0.66, and total GH was 1.35 ± 0.66. At 6m, each of these parameters had significantly increased to 0.36 ± 0.21, 1.8 ±0.74 and 2.2 ±0.89 respectively (p values from 0.02-0.04). Similar significant increases were seen for LUM-201 3.2mg/kg/d. Combining the data from both LUM-201 doses demonstrated that GH secretion determined by deconvolution analysis was 3.3-4.0 µg/kg/24hrs compared to 5 µg/kg/24hrs derived from published data on normal children (Zadik et al, Horm Res 1992), indicating restoration of GH secretion by LUM-201. These values are considerably less than 25-34µg/kg/d of recombinant human GH used in the treatment of PGHD. At 6m, the annualized height velocity (AHV) was 7.2cm/yr for the LUM-201 1.6mg/kg/d and 8.1cm/yr for the 3.2 mg/kg/d dose. At 12m, AHV for a subset was 6.9cm/yr for the 1.6 dose and 7.2cm/yr for the 3.2 dose. Baseline IGF-1 SDS (mean ±SD) were -1±0.63 in 1.6mg/kg/d group & -0.85±0.47 in 3.2mg/kg/d group. The change over 12m was +0.9 on 1.6 dose and +1.1 on 3.2 dose, indicating similar efficacy for IGF-1 generation. LUM-201 showed good tolerability in this study, with no observed safety concerns in adverse events (AEs), labs, and ECGs. Conclusions: At 6m LUM-201 was able to restore endogenous GH pulsatile secretion to a similar level to that seen in normal children, while normalizing serum IGF-1 concentrations. These results indicate that by restoring endogenous GH secretion, LUM-201 facilitates growth utilizing a much lower amount of GH than that provided by daily exogenous rhGH administration. Presentation: 6/3/2024