SKYTROFA

What it is

Skytrofa consists of somatropin transiently conjugated to a methoxypolyethylene glycol carrier via a proprietary TransCon Linker. Lonapegsomatropin is a long-acting prodrug of somatropin (recombinant human growth hormone). After subcutaneous administration, lonapegsomatropin releases fully active somatropin via autocleavage of the TransCon Linker. Somatropin derived from lonapegsomatropin has the same mode of action and distribution as daily somatropin, but with a once-weekly subcutaneous injection.

Approved indications

— Growth failure in children and adolescents aged from 3 years up to 18 years due to insufficient endogenous growth hormone secretion.

Dosing overview

The recommended starting dose of Skytrofa is 0.24 mg somatropin/kg body weight, given once weekly. The dosage and administration should be individualised for each patient. The dose of lonapegsomatropin should be individually adjusted for each patient based on clinical response, adverse reactions, and serum insulin-like growth factor-1 (IGF-1) concentrations outside the targeted range. Each injection should be administered subcutaneously once-weekly in the abdomen, buttock or thigh. If a dose is missed, it should be administered as soon as possible and no more than 2 days after the missed dose. If more than 2 days have passed, the missed dose should be skipped, and the next dose should be administered on the regularly scheduled day.

Key safety warnings

Anaphylactic reactions including angioedema have been reported with the use of lonapegsomatropin. Inform patients and caregivers that such reactions can occur, particularly after first dose, and that prompt medical attention should be sought if a sudden serious hypersensitivity reaction occurs. In patients with previous malignant disease, special attention should be given to signs and symptoms of relapse. Patients with pre-existing tumours or GHD secondary to an intracranial lesion should be examined routinely for progression or recurrence of the underlying disease process. In childhood cancer survivors, an increased risk of a second neoplasm has been reported in patients treated with growth hormone after their first neoplasm. Intracranial tumours, in particular meningiomas, were the most common form of a second neoplasm reported in patients treated with radiation to the head for their first neoplasm. In case of severe or recurrent ataxia, headache, visual problems, nausea and/or vomiting, a funduscopy for papilloedema is recommended. If papilloedema is confirmed, a diagnosis of benign intracranial hypertension should be considered and, if appropriate, growth hormone treatment should be discontinued. Growth hormone may reduce insulin sensitivity. For patients with diabetes mellitus, the insulin dose may require adjustment after lonapegsomatropin therapy is instituted. Patients with diabetes mellitus, glucose intolerance, or additional risk factors for diabetes mellitus should be monitored closely during lonapegsomatropin therapy.

Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. Lonapegsomatropin must not be used when there is any evidence of activity of a tumour. Intracranial tumours must be inactive and anti-tumour therapy must be completed prior to starting growth hormone therapy. Patients with acute critical illness suffering complications following open heart surgery, abdominal surgery, multiple accidental trauma, acute respiratory failure or similar conditions must not be treated with lonapegsomatropin. Lonapegsomatropin must not be used for growth promotion in children with closed epiphyses.

Regulatory history

Skytrofa was registered on the ARTG on 23 May 2025 across nine product strengths ranging from 3 mg to 13.3 mg somatropin. The TGA approved Skytrofa (lonapegsomatropin) for the treatment of growth failure in children and adolescents aged 3 to 18 years due to insufficient endogenous growth hormone secretion on 20 May 2025. This decision reflects the drug's potential to offer a less frequent, weekly dosing regimen compared to daily treatments. Lonapegsomatropin is a long-acting prodrug designed to reduce the dosing frequency for growth hormone deficiency treatment from daily to weekly, aiming to address the burden of daily administration and improve adherence.