FDA Approved Growth Hormone Axis

Lonapegsomatropin

also known as: Skytrofa, TransCon hGH, TransCon growth hormone, ACP-011, lonapegsomatropin-tcgd

Ascendis Pharma's once-weekly growth hormone prodrug (Skytrofa) — the first weekly GH to receive FDA approval (August 2021) for pediatric GH deficiency in patients aged 1+ years weighing at least 11.5 kg.

A once-weekly prodrug of recombinant human somatropin in which native, unmodified hGH is transiently conjugated to a 40 kDa methoxy-PEG carrier through a self-cleaving linker that hydrolyzes at physiologic pH to release unmodified somatropin at a controlled rate over approximately one week. FDA-approved as Skytrofa in August 2021 for pediatric GH deficiency — the first weekly GH formulation approved in the US and notable for releasing bioidentical native somatropin (rather than a modified analog) from the depot.

Mechanism of action

Transient conjugation (TransCon) platform: somatropin is covalently linked to a 40 kDa methoxy-PEG carrier via a β-eliminative self-cleaving linker. At physiologic pH and temperature, the linker autohydrolyzes at a predictable rate, releasing native unmodified somatropin into circulation. The released somatropin has the same pharmacology as daily somatotropin but delivered as a continuous low-amplitude infusion rather than a pulsatile pharmacologic dose.

Primary uses

  • Pediatric growth hormone deficiency (age 1+, weight ≥11.5 kg)

Typical dosing

0.24 mg/kg/week once weekly (subcutaneous)

Fixed weekly dosing 0.24 mg/kg/week; rotated injection sites. Notable for producing a smoother IGF-1 profile than daily somatropin due to the continuous release kinetics.

Regulatory status

FDA-approved August 2021 as Skytrofa (Ascendis Pharma) for the treatment of pediatric patients one year and older who weigh at least 11.5 kg and have growth failure due to inadequate secretion of endogenous growth hormone. EMA approval January 2022. Ascendis has additional programs exploring adult GHD and other indications.

References

  1. [fda-pi] Skytrofa (lonapegsomatropin-tcgd) Prescribing Information. Ascendis Pharma.
  2. [clinical-trial] Thornton PS, et al. "Weekly Lonapegsomatropin in Treatment-Naïve Children With Growth Hormone Deficiency: The Phase 3 heiGHt Trial." J Clin Endocrinol Metab, 2021;106:3184-3195.
  3. [manufacturer] Ascendis Pharma. "Ascendis Pharma announces FDA approval of Skytrofa." Press release, August 25, 2021.

Related peptides

Somatropin (HGH)

FDA-approved recombinant human growth hormone — the direct hormone replacement, with multiple clinical indications, prescription-only status, and specific federal criminal provisions against off-label distribution.

Somapacitan

Novo Nordisk's once-weekly growth hormone (Sogroya) — FDA-approved in 2020 for adult GH deficiency and in 2023 for pediatric GH deficiency in children aged 2.5+ years.

Somatrogon

Pfizer/OPKO's once-weekly growth hormone (Ngenla) — FDA-approved in June 2023 for pediatric GH deficiency in children aged 3+ years; uses a CTP-fusion strategy borrowed from long-acting follitropin alfa.

Sermorelin

The N-terminal 29 amino acids of native GHRH — a former FDA-approved diagnostic and pediatric GH-deficiency therapy, now widely compounded for adult anti-aging protocols.
Disclaimer

This entry is for educational purposes only and does not constitute medical advice. Dosing information reflects published regulatory or research data and is not a recommendation. Many compounds described here are not approved for human use in the United States. Consult a licensed medical professional before considering any peptide therapy.