Lonapegsomatropin

Long Acting Growth Hormone Analog (PEGylated Recombinant Human Growth Hormone)Rx: PrescriptionCompound: Approved

Also known as: lonapegsomatropin-tcgd, PEG-hGH prodrug, SKYTROFA, TransCon hGH

Educational Only — Not medical advice. Consult a qualified clinician before using any peptide.

Summary

Lonapegsomatropin (brand name SKYTROFA) is a once-weekly, long-acting PEGylated prodrug of somatropin approved for the treatment of pediatric growth hormone deficiency (GHD). It was developed by TransCon Therapeutics and approved by the FDA in 2021 for patients ≥1 year old who weigh ≥11.5 kg. Its extended half-life allows weekly dosing compared to the daily injections required for conventional somatropin.

Mechanism of Action

Lonapegsomatropin is a prodrug consisting of recombinant human growth hormone (somatropin) conjugated to a 30 kDa polyethylene glycol (PEG) moiety via a transient linker. After subcutaneous administration, the PEG moiety is cleaved by endogenous esterases, releasing the active somatropin. Somatropin binds to and activates growth hormone receptors, stimulating IGF-1 production in the liver and peripheral tissues, promoting linear growth and anabolic metabolic effects.

Routes of Administration

Subcutaneous

Goals & Uses

  • Normalization of IGF-1 levelsBiomarker / MetabolicHigh
  • Adult growth hormone deficiency (investigational)EndocrinologyModerate
  • Treatment of pediatric growth hormone deficiencyEndocrinology / GrowthHigh
  • Improved treatment adherence via weekly dosingPatient Convenience / AdherenceHigh

Contraindications

  • Active malignancyOncologyHighUse caution or avoid depending on agent and context
  • Acute critical illnessCritical CareHigh
  • Closed epiphyses (for growth promotion indication)Pediatric / SkeletalModerate
  • Hypersensitivity to somatropin or PEG componentsAllergy / ImmunologyHigh
  • Diabetic retinopathyOphthalmologyModerate
  • Prader-Willi syndrome with severe obesity or respiratory impairmentGenetic SyndromeHigh

Adverse Effects

  • Intracranial hypertension (benign)NeurologicalRare
  • Injection site reactionsLocalCommon
  • HeadacheNeurologicCommonPain in the head or upper neck
  • Elevated IGF-1 levels (above normal range)Endocrine / MetabolicCommon
  • Slipped capital femoral epiphysisMusculoskeletalRare
  • HypothyroidismEndocrineUncommon

Drug Interactions

  • GlucocorticoidsModerate
  • Cytochrome P450 substrates (e.g., cyclosporine, sex hormones, anticonvulsants)Low
  • Insulin and antidiabetic agentsModerate
  • Thyroid hormone replacementModerate

Population Constraints

  • Adults (off-label use)AdultRelative
  • Patients with diabetes mellitusMetabolicRelative
  • Pediatric patients <1 year or weighing <11.5 kgPediatricAbsolute
  • Patients with History of MalignancyOncologyRelative

Regulatory Status

  • European UnionApprovedApproved: Pediatric growth hormone deficiencyEMA approved March 2022. Marketed as SKYTROFA in the European Union.
  • United StatesApprovedApproved: Pediatric growth hormone deficiency in patients ≥1 year old weighing ≥11.5 kgFDA approved August 25, 2021. Marketed as SKYTROFA. Orphan drug designation granted.
  • United KingdomApprovedApproved: Pediatric growth hormone deficiencyMHRA approved following EMA decision; available in the UK market.

FDA approved August 2021 for pediatric GHD. EMA approved March 2022 (marketed as SKYTROFA in EU). Dosed once weekly subcutaneously; dose based on body weight.

Evidence & Sources

No sources recorded yet.

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