Lonapegsomatropin
A once-weekly prodrug of somatropin using TransCon technology, approved for pediatric GH deficiency. It releases unmodified GH gradually from a pegylated carrier, matching daily GH exposure with weekly dosing.
01 Overview
Lonapegsomatropin (brand Skytrofa) is a long-acting GH prodrug in which somatropin is transiently bound to a methoxy-PEG carrier via a TransCon linker that releases active, unmodified GH at physiologic pH and temperature. This produces sustained GH exposure from a single weekly injection.
The phase 3 heiGHt trial showed non-inferior, numerically higher annual height velocity versus daily somatropin in treatment-naive children. It is FDA-approved for pediatric GHD and is a well-characterised modern long-acting GH.
02 Mechanism
A PEG-carrier prodrug that slowly releases native somatropin, which then activates the GH receptor; the linker chemistry, not GH modification, provides the long duration.
03 Dosing
| Tier | Dose | Route | Notes |
|---|---|---|---|
| Pediatric GHD | 0.24 mg/kg/wk | SubQ | Once weekly, as approved for pediatric GH deficiency. |
04 Effects
| Effect | Magnitude | Evidence | |
|---|---|---|---|
| Increased height velocityNon-inferior and numerically higher growth versus daily GH in the heiGHt trial. | ~11.2 cm/yr | Clinical | |
| Weekly dosing convenienceReduces injection frequency versus daily somatropin. | 7 to 1 injections/week | Clinical |
05 Side effects
| Effect | Severity | Frequency | Evidence | Countermeasures |
|---|---|---|---|---|
| Injection-site reactionsLocal redness, pain or swelling. | Mild | Common | Clinical | |
| Transient hyperglycaemiaGH-related glucose elevation. | Mild | Uncommon | Clinical |