ORAGROWTH210 TRIAL (PHASE 2): ORAL LUM-201 SHOWS SIMILAR ANNUALIZED HEIGHT VELOCITY TO DAILY RHGH IN MODERATE PEDIATRIC GROWTH HORMONE DEFICIENCY (PGHD) WITH A 1.6MG/KG/DAY DOSE AND A PROMISING INVESTIGATIONAL SAFETY RECORD

Abstract

The primary objective is to evaluate the safety and efficacy of oral LUM-201 at 0.8, 1.6, or 3.2 mg/kg/day in pre-pubertal moderate PGHD subjects. LUM-201, a potent, oral investigational growth hormone (GH) Secretagogue Receptor 1a agonist, uses a predictive enrichment marker (PEM) to identify moderate PGHD patients likely to respond. PEM+ criteria include baseline insulin-like growth factor-1 (IGF-1) level >30 ng/mL & a peak GH of ≥5 ng/mL post LUM-201 single 0.8 mg/kg dose. The OraGrowtH210 Trial, a global study, randomized 81 PEM+ (36F) moderate PGHD subjects in 4 arms: 3 LUM-201 doses & daily recombinant human GH (rhGH) 34 μg/kg/day. Safety & growth responses were analyzed at 6 & 12 months (m). At 6m, least square mean (LSM) annualized height velocity (AHV) for LUM-201 dosed at 0.8, 1.6, or 3.2 mg/kg/day were 7.1, 8.2, & 7.6 cm/yr, respectively; rhGH arm 10.0 cm/yr. At 12m, LSM AHV were 6.8, 8.0, 7.3 cm/yr, respectively, and rhGH arm was 9.7 cm/yr. LUM-201 1.6 mg/kg/day dose produced the highest LSM AHV of 8.2 cm/yr (6m) & 8.0 cm/yr (12m) in moderate PGHD subjects. Normalization of IGF-1 levels occurred within 6m and was sustained through 12m in the per protocol population. At 6m, changes from baseline SDS were 1.01±0.69 (0.8 dose), 1.08±0.57 (1.6 dose), 1.32±0.86 (3.2 dose), & 1.47±0.66 (rhGH). Through 12m, IGF-1 SDS values were maintained at near-normal levels of -0.48±1.36 (0.8 dose), -0.21±0.81 (1.6 dose), +0.14±0.96 (3.2 dose), & +0.74±1.44 (rhGH). LUM-201 exhibited good investigational tolerability, with no observed safety signals in adverse events (AEs), labs, ECGs, & no instances of study discontinuation due to LUM-201-related serious AEs. LUM-201 at 1.6 mg/kg dose had the highest AHV with favorable investigational safety and tolerability and was comparable to daily rhGH aligning with expectations for the moderate PGHD population based on historical data, and within historical FDA criteria for lack of inferiority in growth. Normalization of IGF-1 within 6 months was sustained at 12 months. Increase in IGF-1 levels is significantly greater in the rhGH arm compared to LUM-201 arms. Thus, GH secretion induced by LUM-201, which we have shown returns GH secretion to levels found in normal children (Cassorla et al ESPE 2023), appears effective in promoting growth and normalizing IGF-1 with GH levels considerably lower than those generated by injectable rhGH dose.