Lumos Pharma Announces New Data and Analysis of 15 Subjects from OraGrowtH212 Trial Presented at the 2023 ESPE Annual Meeting - Seite 2

The objective of the analysis was to characterize growth hormone (GH) profiles, defined by deconvolution analysis, based on the GH concentration sampled over 12 hours at baseline and after 6 months of therapy with daily oral LUM-201 to illustrate how LUM-201 increases annualized height velocity (AHV), total GH secretion, and serum IGF-1 and IGFBP3 in individuals with moderate PGHD. Fifteen prepubertal, naive moderate PGHD subjects were screened with a predictive enrichment marker (PEM) test to assess their acute response to oral LUM-201 (0.8mg/kg), with a positive test having a peak GH ≥5 ng/ml with a basal IGF-1 >30 ng/ml. At baseline, subjects (10M:5F) were (mean ± SD) aged 7.9±1.4 years, with IGF-1 SDS -0.82±0.9, and peak GH 7.2±2.2 ng/mL (clonidine stimulation), consistent with moderate PGHD.

Deconvolution analysis was performed on serum GH measured every 10 minutes (0800 h to 2000 h). Patients were randomized to receive 1.6 mg/kg/day or 3.2 mg/kg/day of oral LUM-201. Both baseline characteristics and acute GH responses to the PEM test (p=0.9) and the day 1 PEM test doses were not different between the groups (34.8±6.6 ng/ml for 1.6mg/kg and 38.2±11.2 ng/ml for 3.2mg/kg, p=0.7). The groups were therefore combined in this analysis.

Results showed that after 6 months of treatment with LUM-201, GH, IGF parameters, and AHV increased 60-80% (see Table 1 for means (SD)) from baseline. The study author concluded that LUM-201 enhanced pulsatile GH secretion to similar levels observed in normal growing children (estimated at ~3.5 μg/kg/12h; Albertsson-Wikland et al JCEM 1994), and that restoration of physiological pulsatile GH secretion and IGF-1 were sufficient to support normal growth. The study’s author further noted that LUM-201 in the potential treatment of moderate PGHD has the advantages of being taken orally, enhancing endogenous pulsatile GH secretion, and therefore maintaining normal feedback mechanisms to restore more physiological growth.

Table 1	Baseline	6 Month	t test, p value
GH total*	1.45 (0.89)	2.32 (1.25)	0.013
GH pulsatile*	1.28 (0.83)	1.93 (1.17)	0.035
GH basal *	0.17 (0.11)	0.40 (0.28)	0.008
AHV (cm/year)	4.7 (1.3)	7.6 (1.1)	< 0.00001
IGF-1 (ng/mL)	115.5 (46.6)	205.4 (63.9)	0.0004
IGFBP3 (nmol/L)	139.3 (32.6)	169.0 (30.1)	0.0004
IGF-1:IGFBP3	0.108 (0.031)	0.157 (0.050)	0.0044
*daytime secretion μg/kg body weight per 12hr