The Australian Therapeutic Goods Administration (TGA) has approved SKYTROFA (lonapegsomatropin) as a once-weekly injectable therapy for pediatric growth hormone deficiency (GHD), marking a significant advancement in treatment options for children with this rare endocrine disorder. The approval covers treatment of "growth failure in children and adolescents aged from 3 years up to 18 years due to insufficient endogenous growth hormone secretion."
Specialised Therapeutics, an independent biopharmaceutical company, announced the registration under an exclusive distribution agreement with Ascendis Pharma A/S covering Australia, New Zealand, Singapore, Malaysia, Brunei, Thailand, and Vietnam. This follows previous approvals by the US FDA in August 2021 and the European Medicines Agency in January 2022.
Addressing Unmet Medical Need in Rare Disease
Growth hormone deficiency affects approximately 2-3 per 10,000 Australians, with an estimated 2,000 children living with the condition. The disorder occurs when the pituitary gland fails to produce adequate levels of growth hormone, which is essential for promoting healthy growth in children. Children with GHD typically experience slow height growth resulting in short stature, and may also suffer from delayed puberty, impaired hair growth, and headaches.
"Beyond short stature, children and adolescents with the condition may experience considerable physical and psychosocial impacts on their daily life, such as poor concentration, decreased strength or muscle development, fatigue, and reduced quality of life," said Carlo Montagner, Chief Executive Officer of Specialised Therapeutics.
Innovative TransCon Technology Platform
SKYTROFA represents a significant technological advancement through Ascendis Pharma's proprietary TransCon platform. The therapy is designed as a prodrug of somatropin that provides sustained release of active, unmodified somatropin over one week, eliminating the need for daily injections that have been the standard of care for decades.
The TransCon technology consists of three components: an unmodified parent drug (somatropin), an inert methyloxypolyethylene glycol carrier (mPEG), and a proprietary TransCon linker that temporarily binds the two elements. While bound, the carrier inactivates the somatropin and shields it from renal excretion and receptor-mediated clearance. Following injection, autocleavage of the linker occurs under physiologic conditions, releasing fully active, unmodified somatropin in a predictable manner.
Clinical Evidence and Safety Profile
The TGA registration was supported by results from three pivotal Phase 3 clinical trials: heiGHt, fliGHt, and enliGHten, which collectively treated more than 300 pediatric patients diagnosed with GHD, including participants from Australia. The heiGHt trial evaluated treatment-naïve patients, fliGHt studied treatment-experienced patients, and enliGHten served as a long-term extension trial, with some patients receiving lonapegsomatropin treatment for over four years.
SKYTROFA demonstrated a generally well-tolerated safety profile across all three clinical trials. The most commonly reported adverse events included viral infections, fever, cough, nausea and vomiting, hemorrhage, diarrhea, abdominal pain, arthralgia, arthritis, and increased blood phosphate levels.
Dosing and Administration
SKYTROFA is available in single-use, prefilled cartridges manufactured in nine dosage strengths, designed for use with the SKYTROFA Auto-Injector. The cartridges can be stored at room temperature for up to six months. The recommended starting dose for treatment-naïve children and those switching from daily somatropin is 0.24 mg/kg body weight, administered once weekly. Doses may be adjusted based on the child's weight and insulin-like growth factor-1 standard deviation score (IGF-1 SDS).
Market Access Considerations
Currently, SKYTROFA is not listed on Australia's Pharmaceutical Benefits Scheme (PBS), which may impact patient access and affordability. This represents a significant milestone for Specialised Therapeutics, marking the second endocrinology therapy the company has successfully registered in Australia, following the approval of YORVIPATH (palopegteriparatide) earlier this year.
The approval of SKYTROFA provides Australian families affected by pediatric growth hormone deficiency with a new treatment option that could significantly improve quality of life by reducing injection frequency while maintaining therapeutic efficacy.
