Long-Acting Growth Hormone for Pediatric Growth Hormone Deficiency

Area of Science:

• Endocrinology
• Pediatrics
• Pharmacology

Background:

• Long-acting growth hormone (LAGH) offers potential adherence and outcome improvements over daily somatropin for growth hormone deficiency (GHD).
• LAGHs are molecularly distinct, possessing unique pharmacokinetic/pharmacodynamic properties impacting efficacy and safety.
• Lonapegsomatropin is the sole LAGH in the US and Europe delivering unmodified somatropin.

Purpose of the Study:

• To conduct a systematic literature review and network meta-analysis comparing the relative efficacy and safety of LAGHs in pediatric GHD.
• To evaluate growth outcomes and safety profiles of available LAGHs against daily somatropin.

Main Methods:

• Bayesian network meta-analysis including five trials, with three contributing to the base case network.
• Comparison of three LAGHs (lonapegsomatropin, somapacitan, somatrogon) against daily somatropin.
• Assessment of annualized height velocity, height standard deviation score (SDS) change, insulin-like growth factor-1 (IGF-1) SDS change, bone age progression, and serious adverse events (SAEs).

Main Results:

• Lonapegsomatropin showed statistically significant higher annualized height velocity and height SDS change at week 52 versus daily somatropin and somapacitan.
• Somatrogon and lonapegsomatropin demonstrated significantly higher IGF-1 SDS changes at week 52 compared to certain comparators; all IGF-1 SDS remained within the normal range.
• No significant differences were observed in bone age-to-chronological age ratio progression or SAEs across treatments.

Conclusions:

• Lonapegsomatropin was the only LAGH associated with improved growth outcomes in this network meta-analysis.
• No significant differences in serious adverse events were detected, though other safety outcomes require further analysis.
• The distinct properties of LAGHs necessitate careful consideration for efficacy and safety in pediatric GHD management.