Growth, IGF-1 and IGFBP-3 Responses to Oral LUM-201 in OraGrowtH210 and OraGrowtH212 Trials in Pediatric Growth Hormone Deficiency (PGHD) over 12 to 24 Months on Treatment

Elzbieta Petriczko; Fernando Cassorla; Group OraGrowtH210 Investigator; Team OraGrowtH212 Research; Aleksandra Bruchey; Christopher Smith; Brincks Erik L.; McKew John C.; Thorner Michael O.; Pitukcheewanont Pisit “Duke”

FC7.6

Prev Next

Section Contents Cite

ESPE Abstracts (2024) 98 FC7.6

ESPE2024 Free Communications GH and IGFs (6 abstracts)

Growth, IGF-1 and IGFBP-3 Responses to Oral LUM-201 in OraGrowtH210 and OraGrowtH212 Trials in Pediatric Growth Hormone Deficiency (PGHD) over 12 to 24 Months on Treatment

Elzbieta Petriczko ¹ , Fernando Cassorla ² , OraGrowtH210 Investigator Group ³ , OraGrowtH212 Research Team ² , Aleksandra Bruchey ³ , Christopher Smith ³ , Erik L. Brincks ³ , John C. McKew ³ , Michael O. Thorner ³ & Pisit “Duke” Pitukcheewanont ³

Views

Author affiliations

¹Sonomed Clinic, Szczecin, Poland. ²Institute of Maternal and Child Research, Santiago, Chile. ³Lumos Pharma, Inc., Austin, USA

Background: LUM-201, a potent long-acting oral GH secretagogue (GHS), acts on the GHS Receptor-1a to induce GH secretion. The best candidates for this investigative oral treatment are pre-pubertal children with moderate GHD (standard stimulation testing peak GH between ≥3 <10ng/ml) that respond positively to the LUM-201 Predictive Enrichment Marker (PEM) test (Bright et al JES, 2021). PEM positive responders have basal serum IGF-1 >30ng/ml and a peak serum GH ≥5ng/ml following a single dose of 0.8 mg/kg LUM-201. The OraGrowtH212 single center trial in Chile (n = 22 enrolled) has shown that 1.6 or 3.2 mg/kg/day of LUM-201 increased basal, pulsatile and total GH secretion (the latter by 92%) at 6 months (m) (Cassorla et al, ESPE 2023). The OraGrowtH210 Trial (n = 82 enrolled), an international multi-center dose-finding study, evaluated LUM-201 doses 0.8, 1.6 and 3.2 mg/kg daily and recombinant human GH (rhGH) at a dose of 34µg/kg/day.

Objectives: To report the growth, IGF-I and IGFBP-3, and safety data in the OraGrowtH210 and OraGrowtH212 studies, combining the 1.6 and 3.2 mg/kg/day doses in children with moderate GHD over 12 to 24m.

Results: Baseline annualized height velocity (AHV, mean ± SD) was 4.5±1.2 cm/yr (n = 38). The 12m AHV was 7.4 ±1.3cm/yr (n = 48) and the 24m AHV was 7.3 ±0.7 cm/yr (n = 12), who remained pre-pubertal. Comparing the % change in AHV between 12 and 24m with LUM-201 to that seen for a comparable GHD cohort (Ranke et al JCEM 2010), there was a 10% decrease for LUM-201 versus 20% for rhGH arm. IGF-I concentrations increased by 95% for LUM-201, compared to 165% for rhGH. For IGFBP-3, the increase for LUM-201 was 34% which was closer to a 51% increase for rhGH. IGF-I & IGFBP-3 levels on LUM-201 were maintained at 24m. LUM-201 demonstrated good investigational tolerability, with no observed safety signals in adverse events, labs, ECGs, and no instances of study discontinuation due to LUM-201-related serious AEs.

Conclusions: LUM-201 in prepubertal moderate PGHD increases AHVs to above the 50th centile for age and sex. Preliminary data suggest such growth rate can be maintained to 24m, with lower fall-off in AHV in the second year compared to that seen with rhGH. Serum IGF-I and IGFBP-3 are increased, with IGF-I levels lower than those induced by rhGH. LUM-201 has a favorable investigational safety profile to date. Oral LUM-201 may provide an innovative way to treat moderate PGHD.