Somatropin pegol

Summary

Somatropin pegol (trade name Lonapegsomatropin, brand SKYTROFA) is a long-acting PEGylated recombinant human growth hormone designed for once-weekly subcutaneous administration. It was developed to replace the daily injections required by conventional somatropin. The PEG moiety is cleaved in vivo to release the active somatropin molecule.

Mechanism of Action

Binds to growth hormone receptors on target cells, activating the JAK2-STAT5 signaling pathway, leading to IGF-1 production in the liver and peripheral tissues, thereby promoting growth, anabolism, and metabolic regulation. PEGylation extends the half-life compared to native somatropin.

Routes of Administration

Goals & Uses

• Adult growth hormone deficiency (investigational)EndocrinologyModerate
• IGF-1 normalizationBiomarker / Surrogate EndpointHigh
• Turner syndrome (investigational)Rare Disease / GrowthLow
• Treatment of pediatric growth hormone deficiencyEndocrinology / GrowthHigh
• Improved treatment adherence via once-weekly dosingPatient Convenience / AdherenceHigh

Contraindications

• Active malignancyOncologyHighUse caution or avoid depending on agent and context
• Acute critical illnessCritical CareHigh
• Hypersensitivity to somatropin or PEG componentsAllergy / ImmunologyHigh
• Active proliferative or severe non-proliferative diabetic retinopathyOphthalmologyHigh
• Closed epiphyses (for growth promotion)EndocrinologyModerate
• Prader-Willi syndrome with obesity or respiratory impairmentGenetic DisorderHigh

Adverse Effects

• Peripheral edemaFluid BalanceUncommonSwelling of the arms or legs
• Injection site reactionsLocalCommon
• Intracranial hypertensionNeurologicalRare
• IGF-1 elevation above normal rangeEndocrine / MetabolicCommon
• Arthralgia / myalgiaMusculoskeletalUncommon
• Glucose intolerance / hyperglycemiaMetabolic / EndocrineUncommon

Drug Interactions

• GlucocorticoidsModerate
• Insulin / Oral antidiabeticsModerate
• CYP450 substrates (narrow therapeutic index)Low
• Sex hormones (estrogens)Moderate

Population Constraints

• Neonates and infants under 1 yearPediatricRelative
• PregnancyReproductive SafetyRelative
• Patients with diabetes mellitusMetabolicRelative
• Patients with History of MalignancyOncologyRelative
• Hypothyroidism (untreated)EndocrineRelative

Regulatory Status

• European UnionApprovedApproved: Pediatric growth hormone deficiencyApproved by EMA as lonapegsomatropin (SKYTROFA) in 2022 for children 3 years and older.
• United StatesApprovedApproved: Pediatric growth hormone deficiency (GHD) in patients 1 year and olderApproved by FDA on August 26, 2021 under the name lonapegsomatropin-tcgd (SKYTROFA). Ascendis Pharma.
• United KingdomUnknownRegulatory status post-Brexit unclear; MHRA review may be pending or ongoing.

Approved by the FDA in August 2021 for treatment of pediatric growth hormone deficiency (GHD) in patients 1 year and older. Also known as lonapegsomatropin or TransCon hGH. Developed by Ascendis Pharma.

Evidence & Sources

No sources recorded yet.