Lonapegsomatropin

SKYTROFA is a pegylated human growth hormone (somatropin) for once-weekly subcutaneous injection [see Clinical Pharmacology (12.3) ] . Somatropin binds to the growth hormone (GH) receptor in the cell membrane of target cells resulting in intracellular signal transduction and a host of pharmacodynamic effects.

• SKYTROFA (lonapegsomatropin-tcgd) is a human growth hormone indicated for the: Treatment of pediatric patients 1 year and older who weigh at least 11.5 kg and have growth failure due to inadequate secretion of endogenous growth hormone (GH). Replacement of endogenous growth hormone in adults with growth hormone deficiency (GHD).

• SKYTROFA is contraindicated in patients with: Acute critical illness after open heart surgery, abdominal surgery or multiple accidental trauma, or those with acute respiratory failure due to the risk of increased mortality with use of pharmacologic doses of somatropin [see Warnings and Precautions (5.1) ] . Hypersensitivity to somatropin or any of the excipients in SKYTROFA.contraindicated

SKYTROFA should be administered subcutaneously once weekly into the abdomen, buttock, or thigh with regular rotation of the injection sites ( 2.7 ). Pediatric Patients: Recommended dose is 0.24 mg/kg body weight once weekly ( 2.2 ). Adults: Recommended starting dose is based on age and concomitant use of oral estrogen. Titrate monthly until the desired clinical response and/or weekly average IGF-1 concentration are achieved ( 2.3 ). See Full Prescribing Information for instructions on preparation and administration of drug ( 2.5 , 2.6 , 2.7 ). 2.1 General Dosing Information For subcutaneous injection, once weekly. Therapy with SKYTROFA should be supervised by a healthcare provider who is experienced in the diagnosis and management of patients with growth hormone deficiency (GHD). Perform fundoscopic examination before initiating treatment with SKYTROFA to exclude preexisting papilledema. If papilledema is identified, evaluate the etiology and treat the underlying cause before initiating treatment with SKYTROFA [see Warnings and Precautions (5.5) ] . 2.2 Recommended Dosage for Pediatric Patients The recommended dose of SKYTROFA for treatment-naïve patients and patients switching from another growth hormone product is 0.24 mg/kg body weight, given once weekly. Individualize and titrate the dosage of SKYTROFA based on response. When changing from daily somatropin therapy to once-weekly SKYTROFA, wait at least 8 hours between the final dose of daily somatropin and the first dose of SKYTROFA.

Severe Hypersensitivity: Hypersensitivity reactions, including anaphylaxis and angioedema have occurred. In the event of an allergic reaction, seek prompt medical attention ( 5.2 ). Increased Risk of Neoplasms: Monitor patients with preexisting tumors for progressions or recurrence. Increased risk of a second neoplasm in childhood cancer survivors treated with somatropin – in particular meningiomas in patients treated with radiation to the head for their first neoplasm ( 5.3 ). Glucose Intolerance and Diabetes Mellitus: May be unmasked. Periodically monitor glucose levels in all patients. Doses of concurrent antihyperglycemic drugs in diabetics may require adjustment ( 5.4 ). Intracranial Hypertension: Exclude preexisting papilledema. May develop and is usually reversible after discontinuation or dose reduction ( 5.5 ). Fluid Retention (i.e., edema, arthralgia, carpal tunnel syndrome): May occur. Reduce dose as necessary ( 5.6 ). Hypoadrenalism: Monitor patients for reduced serum cortisol levels and/or need for glucocorticoid dose increases in those with known hypoadrenalism ( 5.7 ). Hypothyroidism: May first become evident or worsen ( 5.8 ). Slipped Capital Femoral Epiphysis in Pediatric Patients: May develop. Evaluate children with the onset of a limp or persistent hip/knee pain ( 5.9 ). Progression of Preexisting Scoliosis: May develop ( 5.10 ). Pancreatitis: Consider pancreatitis in patients with persistent severe abdominal pain ( 5.11 ).

The following important adverse reactions are described elsewhere in the labeling: Increased mortality in patients with acute critical illness [see Warnings and Precautions (5.1) ] Severe hypersensitivity [see Warnings and Precautions (5.2) ] Increased risk of neoplasms [see Warnings and Precautions (5.3) ] Glucose intolerance and diabetes mellitus [see Warnings and Precautions (5.4) ] Intracranial hypertension [see Warnings and Precautions (5.5) ] Fluid retention [see Warnings and Precautions (5.6) ] Hypoadrenalism [see Warnings and Precautions (5.7) ] Hypothyroidism [see Warnings and Precautions (5.8) ] Slipped capital femoral epiphysis in pediatric patients [see Warnings and Precautions (5.9) ] Progression of preexisting scoliosis in pediatric patients [see Warnings and Precautions (5.10) ] Pancreatitis [see Warnings and Precautions (5.11) ] Lipoatrophy [see Warnings and Precautions (5.12) ] Sudden death in pediatric patients with Prader-Willi syndrome [see Warnings and Precautions (5.13) ] Pediatric Patients: Most common adverse reactions (≥ 5%): viral infection, pyrexia, cough, nausea and vomiting, hemorrhage, diarrhea, abdominal pain, and arthralgia and arthritis ( 6.1 ). Adults: Most common adverse reaction (≥ 5%): edema peripheral ( 6.1 ). To report SUSPECTED ADVERSE REACTIONS, contact Ascendis Pharma Endocrinology, Inc., at 1-844-442-7236 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

8.1 Pregnancy Risk Summary There are no available data on lonapegsomatropin-tcgd use in pregnant patients to evaluate a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. Available published data over several decades for somatropin, the active component of lonapegsomatropin-tcgd, have not identified a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. In animal reproduction studies, there was no evidence of embryo-fetal or neonatal harm when pregnant rats were administered subcutaneous lonapegsomatropin-tcgd at doses up to 13-fold the clinical pediatric dose of 0.24 mg/kg/week and approximately 30-fold the maximum clinical therapeutic dose for adult GHD of 6.3 mg hGH/week (see Data ) . The estimated background risk of birth defects and miscarriages for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriages in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Metabolism

Absorption Following subcutaneous dose administration, SKYTROFA releases fully active somatropin via autocleavage of the TransCon linker that follows first-order kinetics. In pediatric patients with GHD, following subcutaneous dose administration of 0.24 mg/kg/week SKYTROFA, the observed mean (CV%) steady-state peak serum concentration (C max ) of lonapegsomatropin-tcgd was 1230 (86.3) ng hGH/mL, and the median time to reach maximum concentrations (T max ) was 25 hours.

Acute overdosage may lead initially to hypoglycemia and subsequently to hyperglycemia. Overdose with somatropin may cause fluid retention. Long-term overdosage may result in signs and symptoms of gigantism consistent with the known effects of excess growth hormone.

• Aug 25, 2021BLABLA761177Ascendis Pharma Encocrinology Div A/s

1. 1Product Dose Omission Issue10719%
2. 2Headache5911%
3. 3Injection Site Pain488.7%
4. 4Device Use Error448.0%
5. 5Device Malfunction315.6%
6. 6Therapy Interrupted264.7%
7. 7Treatment Noncompliance264.7%
8. 8Incorrect Dose Administered234.2%
9. 9Nausea234.2%
10. 10Off Label Use224.0%
11. 11Vomiting224.0%
12. 12Wrong Technique In Device Usage Process183.3%
13. 13Fatigue173.1%
14. 14Liquid Product Physical Issue173.1%
15. 15Rash152.7%

The 8 most recently updated of 8 ClinicalTrials.gov registrations naming Lonapegsomatropin as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• Trial Investigating the Efficacy and Safety of Weekly Lonapegsomatropin Compared to Daily Somatropin in Children and Adolescents With Short Stature or Growth Failure Due to Growth Hormone Sufficient Disorders
  Recruiting · Phase 3 · Interventional · 186 enrolled · Ascendis Pharma A/S
  NCT07221851updated 2026-05-29
• A Trial to Investigate Different Doses of Lonapegsomatropin Compared to Somatropin in Individuals With Turner Syndrome
  Active not recruiting · Phase 2 · Interventional · 48 enrolled · Ascendis Pharma Endocrinology Division A/S
  NCT05690386updated 2026-05-13
• A US Non-interventional, Effectiveness and Safety Study of Patients Treated With SKYTROFA
  Recruiting · Observational · 900 enrolled · Ascendis Pharma Endocrinology Division A/S
  NCT05820672updated 2026-04-21
• A Phase 2 Clinical Trial to Evaluate Efficacy, Safety, and Tolerability of Navepegritide in Combination With Lonapegsomatropin in Children With Achondroplasia
  Active not recruiting · Phase 2 · Interventional · 22 enrolled · Ascendis Pharma Growth Disorders A/S
  NCT06433557updated 2026-02-18
• A Post-Authorisation Safety Study (PASS) of Patients Treated With Lonapegsomatropin
  Recruiting · Observational · 500 enrolled · Ascendis Pharma Endocrinology Division A/S
  NCT05775523updated 2026-02-04
• A Trial to Investigate Long Term Efficacy and Safety of Lonapegsomatropin in Adults With Growth Hormone Deficiency
  Completed · Phase 3 · Interventional · 220 enrolled · Ascendis Pharma Endocrinology Division A/S
  NCT05171855updated 2026-01-09
• A Trial to Compare the Efficacy and Safety of Once-weekly Lonapegsomatropin With Placebo and a Daily Somatropin Product in Adults With Growth Hormone Deficiency
  Completed · Phase 3 · Interventional · 264 enrolled · Ascendis Pharma Endocrinology Division A/S
  NCT04615273updated 2025-01-15
• Safety, Tolerability and Efficacy of TransCon hGH Weekly Versus Daily hGH in Chinese Pediatric Growth Hormone Deficiency
  Unknown · Phase 3 · Interventional · 150 enrolled · Visen Pharmaceuticals (Shanghai) Co., Ltd.
  NCT04326374updated 2020-03-30

Frequently asked questions

How does Lonapegsomatropin work?

SKYTROFA is a pegylated human growth hormone (somatropin) for once-weekly subcutaneous injection [see Clinical Pharmacology (12.3) ] . Somatropin binds to the growth hormone (GH) receptor in the cell membrane of target cells resulting in intracellular signal transduction and a host of pharmacodynamic effects.

What is Lonapegsomatropin used for?

According to FDA labeling, Lonapegsomatropin carries indications including: SKYTROFA (lonapegsomatropin-tcgd) is a human growth hormone indicated for the: Treatment of pediatric patients 1 year and older who weigh at least 11.5 kg and have growth failure due to inadequate secretion of endogenous growth hormone (GH). Replacement of endogenous growth hormone in adults with growth hormone deficiency (GHD).. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Lonapegsomatropin?

Lonapegsomatropin is classified as Somatropin and somatropin agonists, Recombinant Human Growth Hormone, Somatotropin Receptor Agonists.

What are the brand names for Lonapegsomatropin?

Lonapegsomatropin is marketed under brand names including Skytrofa.

What are the contraindications for Lonapegsomatropin?

Lonapegsomatropin labeling lists contraindications including: SKYTROFA is contraindicated in patients with: Acute critical illness after open heart surgery, abdominal surgery or multiple accidental trauma, or those with acute respiratory failure due to the risk of increased mortality with use of pharmacologic doses of somatropin [see Warnings and Precautions (5.1) ] . Hypersensitivity to somatropin or any of the excipients in SKYTROFA.. Always consult the full prescribing information and a clinician.