LUM-201’s unique ability to augment the natural pulsatile secretion of GH

[madman]

https://investors.lumos-pharma.com/news-releases/news-release-details/lumos-pharma-announces-new-analyses-phase-2-oragrowth212-trial

“The new analyses of data from our OraGrowtH212 Trial further characterized LUM-201’s unique ability to augment the natural pulsatile secretion of growth hormone, producing comparable growth to injectable rhGH with significantly less exposure to circulating growth hormone,” said John C. McKew, PhD, President and Chief Scientific Officer of Lumos Pharma. “The presented results also provide additional support for our planned approach to a placebo-controlled Phase 3 trial of LUM-201 in moderate PGHD, a trial design proposed by the FDA as an appropriate option for oral LUM-201 given its differentiated mechanism as a growth hormone secretagogue.”​

In the poster MON-111, titled, 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 (Cassorla, F, et al) [poster link], investigators evaluated growth hormone pulsatility data obtained at baseline and at six months following treatment with LUM-201.​

• Results showed that at six months on LUM-201, a significant increase over baseline in key parameters was observed for the 1.6 mg/kg/day dose. At baseline GH secretion was 0.19 ±0.09 μg/kg/12-hrs; pulsatile GH was 1.17 ±0.66 μg/kg/12-hrs; and total GH was 1.35 ±0.66 μg/kg/12-hrs.
• At 6 months each parameter increased significantly: GH secretion to 0.36 ±0.21 μg/kg/12-hrs, pulsatile GH to 1.8 ±0.74 μg/kg/12-hrs, and total GH to 2.2 ±0.89 μg/kg/12-hrs
• A similar level of increase was observed in the 3.2 mg/kg/day dose cohort
• Investigators combined data from both dose cohorts and conducted a deconvolution analysis on GH secretion. It was determined that at six months GH secretion was 3.3 ±1.8 to 4.4 ±2.1 μg/kg/day compared to 5.0 ±1.3 μg/kg/day derived from published data in normal children, indicating restoration of approximately normal GH secretion by LUM-201.
• Conclusion – at 6 months LUM-201 was able to restore endogenous GH pulsatile secretion to a similar level seen in normal children while also normalizing serum IGF-1 concentrations. 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. By providing an oral therapy that attains physiological GH profiles, investigational LUM-201 treatment aligns with the fundamental objectives of endocrine therapies, specifically the restoration of normal hormonal homeostasis.

 

[madman]

In a late-breaking poster (MON-704) titled, Growth Response to Oral Growth Hormone Secretagogue LUM-201 in Children with Moderate GH Deficiency (GHD) is Dependent on the Pattern of Pulsatile GH Secretion Stimulated by LUM-201 (Stevens, A, et al), [poster link], investigators evaluated pulsatile GH profiles and growth response to LUM-201.​

• Data from OraGrowtH212 pulse assessments at Day 1 (D1) and at 6 months (M6) were analyzed utilizing a univariate Spearman’s rank correlations matrix to screen for relationships between D1 characteristics, D1 height velocity, 6M Annualized Height Velocity and interpulse, pulsatile, and total GH secretion at D1 and M6.
• The 12-hour pattern of pulsatile secretion was characterized using Functional Principal Component Analysis (FPCA) to identify dominant modes of variation in the functional data. Subjects were grouped into tertiles based on 6M AHV. The 12-hour profiles were grouped into three 4-hour intervals.
• Results:
  • All parameters increased from D1 to M6
  • D1 pulsatile GH secretion was positively associated with D1 AHV
  • While 6M AHV increased compared to baseline, GH Secretion at D1 and M6 was not apparently correlated with 6M AHV
  • In the FPCA, difference in interquartile range (IQR) for mean GH secretion was highest in 0-4 hrs in subjects in the high and medium AHV tertiles, while subjects with low AHV at 6 months had the highest difference at 8-12 hours
• Conclusions – LUM-201 stimulates significant increases in GH secretion over 6 months in patients with moderate PGHD. The relationship between growth response and both the amount and pattern of pulsatile GH secretion, with the highest growth observed in OraGrowtH212 associated with greatest pulsatile activity early in the 12 hour profile. Restoring GH secretion with LUM-201 in moderate PGHD results in both an increase in the overall amount of GH, and importantly, an alteration of the pattern of the pulse profile, with distinct differences in these patterns between the best and lower responders.

 

[madman]

The data and potential of LUM-201 (ibutamoren)

Andrew Dauber, M.D., Chief of Endocrinology, Children's National Medical Center, Washington, D.C. discusses the data and potential of LUM-201 for children living with moderate pediatric growth hormone deficiency

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LUM-201 (ibutamoren) - The OraGrowtH212 trial

The OraGrowtH212 trial is a global study involving 80 patients in four arms, testing three different doses of a new drug compared to the standard dose of growth hormone. The study aims to measure catchup growth over an extended period, with promising interim results indicating comparable growth...

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