Growth Response to LUM-201 in the OraGrowtH210 Trial in Idiopathic Pediatric Growth Hormone Deficiency (iPGHD): Interim Analysis Data (41 subjects)

Abstract

Objectives To study safety and efficacy of LUM-201 at 3 different doses (0.8, 1.6, or 3.2 mg/kg/day). LUM-201 (ibutamoren), a growth hormone (GH) Secretagogue Receptor 1a (GHSR1a) agonist, is a potent, investigational oral GH secretagogue currently studied in 3 Idiopathic Pediatric GH Deficiency (iPGHD) Phase 2 trials. The LUM-201 predictive enrichment marker (PEM) is used to identify patients diagnosed with iPGHD 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. Methods The OraGrowtH210 Trial is a 24-month, multi-center Phase 2 trial, open label, randomizing 80 iPGHD PEM+ subjects to 4 arms including 3 LUM-201 doses (0.8, 1.6, or 3.2 mg/kg/day) and daily recombinant human GH (rhGH) at 34 μg/kg/day. This interim analysis (IA) subset of 41(16 F) subjects evaluated the safety and growth response data of LUM-201 in 6, 9, 12-month intervals. Results The mean calculated annual height velocity (AHV) at 6 months of LUM-201 at 0.8, 1.6, or 3.2 mg/kg/day was 7.3, 8.6, 7.8 cm/yr respectively (Fig1). The AHV of LUM-201 appeared to be highest at 1.6 mg/kg dose, and appears to match the predicted AHV on rhGH in this moderate iPGHD population based on several published studies. However, the daily rhGH arm AHV was higher at 11.05 cm/yr. This unexpected growth was likely due to robust growth response from the youngest two subjects in the rhGH cohort who at grew at >99th and >97th percentile (15.6 and 12.7 cm/yr), as well as some imbalance of factors predicting better growth in the rhGH cohort, including 9-month younger age, lower height, greater MPH, much higher BMI SDS, and a higher percentage of males. AHV was also observed at 9- and 12-month time points in smaller number of subjects (Fig1). LUM-201 was well tolerated by subjects in this study period. No safety signal was observed based on AEs, labs and ECGs, and there were no serious AEs related to LUM- 201 and no subject discontinued from this study. Conclusions This IA of the 6-month to 12-month AHV shows 1.6 mg/kg/day dose has the highest growth response with the mean AHV at 6 months of 8.6 cm/yr which is in line with the expectations of 8.3 cm/year AHV observed after 12 months of recombinant growth hormone (rhGH) treatment in a moderate naïve-to-treatment PGHD patient population derived from the large 20-year Phase 4 Eli Lilly GeNeSIS database and other studies. LUM-201 overall was well-tolerated. .