Identification
- Summary
Lonapegsomatropin is a human growth hormone indicated in the treatment of growth failure due to inadequate endogenous growth hormone secretion.
- Brand Names
- Skytrofa
- Generic Name
- Lonapegsomatropin
- DrugBank Accession Number
- DB16220
- Background
Lonapegsomatropin, also known as TransCon hGH or ACP 001, is a methoxypegylated prodrug of human growth hormone (somatropin) indicated for the treatment of children 1 year and older, weighing at least 11.5 kg, with growth failure due to insufficient growth hormone secretion.1,3,4 Unlike somatropin, which requires daily dosing, lonapegsomatropin can be administered as a single weekly dose.3,5
Lonapegsomatropin was granted FDA approval on 25 August 2021.3 It was later approved by the European Commission on 13 January 2022.7
- Type
- Biotech
- Groups
- Approved, Investigational
- Synonyms
- Lonapegsomatropin
- lonapegsomatropin-tcgd
- RhGH-PEG
- Transconpeg hGH
- Transconpeg-hGH
- External IDs
- ACP-011
Pharmacology
- Indication
In the US, lonepegsomatropin is indicated in the treatment of growth failure due to inadequate growth hormone secretion in patients one year and older who weigh at least 11.5 kg.3 In Europe, lonepegsomatropin is indicated to treat growth failure in children and adolescents aged from three years up to 18 years due to insufficient endogenous growth hormone secretion or growth hormone deficiency.8
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Treatment of Growth failure •••••••••••• ••••••••••• ••••••••• ••••••••• Treatment of Growth failure •••••••••••• ••••••••• •••• •••••• ••••• •• ••••••••• - Contraindications & Blackbox Warnings
Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API- Pharmacodynamics
Lonapegsomatropin-tcgd is a growth hormone prodrug indicated in the treatment of growth failure due to inadequate growth hormone secretion in patients 1 year and older who weigh at least 11.5 kg.3 It has a long duration of action as it is given weekly.3 Patients and carers should be counselled regarding the risks of severe hypersensitivity, neoplasms, glucose intolerance, intracranial hypertension, fluid retention, hypoadrenalism, hypothyroidism, slipped capital femoral epiphysis, progression of preexisting scoliosis, and pancreatitis.3
- Mechanism of action
Lonapegsomatropin-tcgd undergoes autocleavage to release active somatropin from the methoxypolyethylene glycol carrier.3 Somatropin binds to the growth hormone receptor leading to direct effects and insulin-like growth factor-1 mediated indirect effects.3 Somatropin has effects on the epiphyses of long bones, leading to growth in pediatric patients.3 Somatropin also stimulates chondrocyte differentiation and proliferation, release of glucose from the liver, protein synthesis, and lipolysis.3
Somatotropin mediates its effects both directly by somatotropin and indirectly by insulin-like growth factor-1 (IGF-1), which is upregulated by growth hormone. It binds to the human growth hormone receptor (GHR), which is a dimeric receptor expressed in target cells in the liver and cartilage.5 Upon binding of growth hormone, GHR dimerizes and interacts with Janus kinase 2 (JAK2), subsequently leading to tyrosine phosphorylation of JAK2 and the GH receptor. The signal transducer activator of transcription (STAT) pathway is initiated, where transcription factors such as STAT1, STAT3, and STAT5 are translocated into the nucleus to stimulate target gene transcription.6
At the epiphysis or growth plate, growth hormone increases linear growth by promoting differentiation of prechondrocytes and expansion of osteoblasts. Growth hormone binding to its receptor in the liver and cartilage promotes the production of IGF-1, which acts on type 1 IGF receptors to also stimulate linear growth. In the liver, activated growth hormone receptor signalling leads to increased production of IGF binding protein-3 (IGFBP-3) and acid-labile subunit (ALS), which are proteins that bind to IGF-1 in a ternary complex to increase its half-life.2
Target Actions Organism AGrowth hormone receptor ligandHumans AProlactin receptor ligandHumans - Absorption
After subcutaneous lonapegsomatropin-tcgd administration, the drug undergoes autocleavage, releasing active somatropin from the methoxypolyethylene glycol carrier.3 0.24 mg/kg/week dosing in pediatric patients leads to a somatropin Cmax of 15.2 ng/mL, with a median Tmax of 12 hours, and a mean AUC of 500 h*ng/mL.3
Methoxypolyethylene glycol reaches a Cmax of 13.1 µg/mL, with a meadian Tmax of 36 hours.3
Human growth hormone (somatropin) concentrations reach a mean steady Cmax of 1230 ng/mL, with a Tmax of 25 hours.3
- Volume of distribution
Lonapegsomatropin-tcgd dosing of 0.24 mg/kg/week leads to a mean steady state apparent volume of distribution of 0.13 L/kg.3
- Protein binding
Not Available
- Metabolism
Lonapegsomatropin-tcgd is a prodrug that undergoes autocleavage, releasing the active somatropin from the methoxypolyethelene glycol carrier.3 The methoxypolyethelene glycol carrier is cleared by the kidneys, while somatropin is metabolized by non-specific protein catabolic pathways in the liver and kidneys to smaller oligopeptides and individual amino acids.3
Hover over products below to view reaction partners
- Route of elimination
The methoxypolyethelene glycol carrier is cleared by the kidneys, while the active somatropin undergoes catabolic processes in the kidneys and liver.3 However, the exact proportions of lonapegsomatropin recovered in the urine and feces has not been reported.
- Half-life
The half life of lonapegsomatropin-tcgd is 30.7 ± 12.7 hours, while the half life of released somatropin was approximately 25 hours.3
- Clearance
In pediatric patients, the apparent clearance of lonapegsomatropin-tcgd is 3.2 mL/h/kg.3
- Adverse Effects
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.- Toxicity
Patients experiencing an acute overdose may present with fluid retention and hypoglycemia followed by hyperglycemia.3 Chronic overdosage may present with signs of gigantism.3 Treat patients with symptomatic and supportive measures.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAcarbose The therapeutic efficacy of Acarbose can be decreased when used in combination with Lonapegsomatropin. Acenocoumarol The metabolism of Acenocoumarol can be increased when combined with Lonapegsomatropin. Acetaminophen The metabolism of Acetaminophen can be increased when combined with Lonapegsomatropin. Acetohexamide The therapeutic efficacy of Acetohexamide can be decreased when used in combination with Lonapegsomatropin. Acyclovir The metabolism of Acyclovir can be increased when combined with Lonapegsomatropin. - Food Interactions
- No interactions found.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Active Moieties
Name Kind UNII CAS InChI Key Somatotropin prodrug NQX9KB6PCL 12629-01-5 Not applicable - International/Other Brands
- Skytrofa (Ascendis Pharma A/S)
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Lonapegsomatropin Ascendis Pharma Injection, powder, for solution 4.3 mg Subcutaneous Ascendis Pharma Endocrinology Division A/s 2022-05-04 Not applicable EU 
Lonapegsomatropin Ascendis Pharma Injection, powder, for solution 11 mg Subcutaneous Ascendis Pharma Endocrinology Division A/s 2022-05-04 Not applicable EU Lonapegsomatropin Ascendis Pharma Injection, powder, for solution 6.3 mg Subcutaneous Ascendis Pharma Endocrinology Division A/s 2022-05-04 Not applicable EU Lonapegsomatropin Ascendis Pharma Injection, powder, for solution 3.6 mg Subcutaneous Ascendis Pharma Endocrinology Division A/s 2022-05-04 Not applicable EU Lonapegsomatropin Ascendis Pharma Injection, powder, for solution 9.1 mg Subcutaneous Ascendis Pharma Endocrinology Division A/s 2022-05-04 Not applicable EU
Categories
- ATC Codes
- H01AC09 — Lonapegsomatropin
- Drug Categories
- Amino Acids, Peptides, and Proteins
- Anterior Pituitary Lobe Hormones and Analogues
- Cytochrome P-450 CYP1A2 Inducers
- Cytochrome P-450 CYP1A2 Inducers (strength unknown)
- Cytochrome P-450 CYP2C19 Inhibitors
- Cytochrome P-450 CYP2C19 Inhibitors (weak)
- Cytochrome P-450 Enzyme Inducers
- Cytochrome P-450 Enzyme Inhibitors
- Growth Hormone
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- P-glycoprotein substrates
- Peptide Hormones
- Peptides
- Pituitary and Hypothalamic Hormones and Analogues
- Pituitary Hormones
- Pituitary Hormones, Anterior
- Prodrugs
- Recombinant Human Growth Hormone
- Somatropin and Somatropin Agonists
- Systemic Hormonal Preparations, Excl. Sex Hormones and Insulins
- Classification
- Not classified
- Affected organisms
- Humans
Chemical Identifiers
- UNII
- OP35X9610Y
- CAS number
- 1934255-39-6
References
- General References
- Thornton PS, Maniatis AK, Aghajanova E, Chertok E, Vlachopapadopoulou E, Lin Z, Song W, Christoffersen ED, Breinholt VM, Kovalenko T, Giorgadze E, Korpal-Szczyrska M, Hofman PL, Karpf DB, Shu AD, Beckert M: Weekly Lonapegsomatropin in Treatment-Naive Children with Growth Hormone Deficiency: The Phase 3 heiGHt Trial. J Clin Endocrinol Metab. 2021 Jul 17. pii: 6323258. doi: 10.1210/clinem/dgab529. [Article]
- Reh CS, Geffner ME: Somatotropin in the treatment of growth hormone deficiency and Turner syndrome in pediatric patients: a review. Clin Pharmacol. 2010;2:111-22. doi: 10.2147/CPAA.S6525. Epub 2010 Jun 1. [Article]
- FDA Approved Drug Products: Skytrofa (Lonapegsomatropin-tcgd) Subcutaneous Injection [Link]
- Clinical Trials: NCT02781727 [Link]
- FDA Approved Drug Products: Norditropin (somatropin) injection, for subcutaneous use [Link]
- StatPearls: Physiology, Growth Hormone [Link]
- BioSpace News: Ascendis Pharma A/S Receives European Approval for TransCon™ hGH for Pediatric Growth Hormone DeficiencyTransCon hGH [Link]
- Summary of Product Characteristics: Lonapegsomatropin subcutaneous injection [Link]
- External Links
- 2569562
- Wikipedia
- Lonapegsomatropin
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count 3 Active Not Recruiting Treatment Adult Onset Growth Hormone Deficiency / Endocrine System Diseases / Hormone Deficiency 1 3 Completed Treatment Endocrine System Diseases / Hormone Deficiency / Human Growth Hormone Deficiency 1 3 Unknown Status Treatment Endocrine System Diseases / Hormones / Human Growth Hormone Deficiency / Pituitary Disease, Anterior / Pituitary Diseases 1 2 Recruiting Treatment Turner's Syndrome 1 Not Available Recruiting Not Available Human Growth Hormone Deficiency 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Injection, powder, for solution Subcutaneous 11 mg Injection, powder, for solution Subcutaneous 13.3 mg Injection, powder, for solution Subcutaneous 3 mg Injection, powder, for solution Subcutaneous 3.6 mg Injection, powder, for solution Subcutaneous 4.3 mg Injection, powder, for solution Subcutaneous 5.2 mg Injection, powder, for solution Subcutaneous 6.3 mg Injection, powder, for solution Subcutaneous 7.6 mg Injection, powder, for solution Subcutaneous 9.1 mg Injection, powder, lyophilized, for solution Subcutaneous 11 mg/1 Injection, powder, lyophilized, for solution Subcutaneous 13.3 mg/1 Injection, powder, lyophilized, for solution Subcutaneous 3 mg/1 Injection, powder, lyophilized, for solution Subcutaneous 3.6 mg/1 Injection, powder, lyophilized, for solution Subcutaneous 4.3 mg/1 Injection, powder, lyophilized, for solution Subcutaneous 5.2 mg/1 Injection, powder, lyophilized, for solution Subcutaneous 6.3 mg/1 Injection, powder, lyophilized, for solution Subcutaneous 7.6 mg/1 Injection, powder, lyophilized, for solution Subcutaneous 9.1 mg/1 - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Liquid
- Experimental Properties
- Not Available
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Ligand
- General Function
- Protein kinase binding
- Specific Function
- Receptor for pituitary gland growth hormone involved in regulating postnatal body growth. On ligand binding, couples to the JAK2/STAT5 pathway (By similarity).The soluble form (GHBP) acts as a rese...
- Gene Name
- GHR
- Uniprot ID
- P10912
- Uniprot Name
- Growth hormone receptor
- Molecular Weight
- 71498.885 Da
References
- Walenkamp MJ, Wit JM: Genetic disorders in the growth hormone - insulin-like growth factor-I axis. Horm Res. 2006;66(5):221-30. [Article]
- Wu XY, Xu Z, Chen C, Liu FK, Li JS: [Correlation of growth hormone receptor expression to preoperative radiosensitivity of rectal cancer patients]. Ai Zheng. 2006 Sep;25(9):1162-7. [Article]
- Adriani M, Garbi C, Amodio G, Russo I, Giovannini M, Amorosi S, Matrecano E, Cosentini E, Candotti F, Pignata C: Functional interaction of common gamma-chain and growth hormone receptor signaling apparatus. J Immunol. 2006 Nov 15;177(10):6889-95. [Article]
- Choi JH, Kim HS, Kim SH, Yang YR, Bae YS, Chang JS, Kwon HM, Ryu SH, Suh PG: Phospholipase Cgamma1 negatively regulates growth hormone signalling by forming a ternary complex with Jak2 and protein tyrosine phosphatase-1B. Nat Cell Biol. 2006 Dec;8(12):1389-97. Epub 2006 Nov 26. [Article]
- Bernstein RM, Leigh SR, Donovan SM, Monaco MH: Hormones and body size evolution in papionin primates. Am J Phys Anthropol. 2007 Feb;132(2):247-60. [Article]
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
- Reh CS, Geffner ME: Somatotropin in the treatment of growth hormone deficiency and Turner syndrome in pediatric patients: a review. Clin Pharmacol. 2010;2:111-22. doi: 10.2147/CPAA.S6525. Epub 2010 Jun 1. [Article]
- FDA Approved Drug Products: Skytrofa (Lonapegsomatropin-tcgd) Subcutaneous Injection [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Ligand
- General Function
- Protein homodimerization activity
- Specific Function
- This is a receptor for the anterior pituitary hormone prolactin (PRL). Acts as a prosurvival factor for spermatozoa by inhibiting sperm capacitation through suppression of SRC kinase activation and...
- Gene Name
- PRLR
- Uniprot ID
- P16471
- Uniprot Name
- Prolactin receptor
- Molecular Weight
- 69505.045 Da
References
- Keeler C, Jablonski EM, Albert YB, Taylor BD, Myszka DG, Clevenger CV, Hodsdon ME: The kinetics of binding human prolactin, but not growth hormone, to the prolactin receptor vary over a physiologic pH range. Biochemistry. 2007 Mar 6;46(9):2398-410. Epub 2007 Feb 6. [Article]
- Ahmed TA, Buzzelli MD, Lang CH, Capen JB, Shumate ML, Navaratnarajah M, Nagarajan M, Cooney RN: Interleukin-6 inhibits growth hormone-mediated gene expression in hepatocytes. Am J Physiol Gastrointest Liver Physiol. 2007 Jun;292(6):G1793-803. Epub 2007 Mar 29. [Article]
- Moderscheim TA, Gorba T, Pathipati P, Kokay IC, Grattan DR, Williams CE, Scheepens A: Prolactin is involved in glial responses following a focal injury to the juvenile rat brain. Neuroscience. 2007 Mar 30;145(3):963-73. Epub 2007 Feb 20. [Article]
- Cunningham BC, Bass S, Fuh G, Wells JA: Zinc mediation of the binding of human growth hormone to the human prolactin receptor. Science. 1990 Dec 21;250(4988):1709-12. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- 11-beta-hydroxysteroid dehydrogenase [nad(p)] activity
- Specific Function
- Catalyzes reversibly the conversion of cortisol to the inactive metabolite cortisone. Catalyzes reversibly the conversion of 7-ketocholesterol to 7-beta-hydroxycholesterol. In intact cells, the rea...
- Gene Name
- HSD11B1
- Uniprot ID
- P28845
- Uniprot Name
- Corticosteroid 11-beta-dehydrogenase isozyme 1
- Molecular Weight
- 32400.665 Da
References
- FDA Approved Drug Products: Skytrofa (Lonapegsomatropin-tcgd) Subcutaneous Injection [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inducer
- General Function
- Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
- Gene Name
- CYP1A2
- Uniprot ID
- P05177
- Uniprot Name
- Cytochrome P450 1A2
- Molecular Weight
- 58293.76 Da
References
- Jurgens G, Lange KH, Reuther LO, Rasmussen BB, Brosen K, Christensen HR: Effect of growth hormone on hepatic cytochrome P450 activity in healthy elderly men. Clin Pharmacol Ther. 2002 Mar;71(3):162-8. doi: 10.1067/mcp.2002.121373. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Steroid hydroxylase activity
- Specific Function
- Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and im...
- Gene Name
- CYP2C19
- Uniprot ID
- P33261
- Uniprot Name
- Cytochrome P450 2C19
- Molecular Weight
- 55930.545 Da
References
- Jurgens G, Lange KH, Reuther LO, Rasmussen BB, Brosen K, Christensen HR: Effect of growth hormone on hepatic cytochrome P450 activity in healthy elderly men. Clin Pharmacol Ther. 2002 Mar;71(3):162-8. doi: 10.1067/mcp.2002.121373. [Article]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Xenobiotic-transporting atpase activity
- Specific Function
- Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
- Gene Name
- ABCB1
- Uniprot ID
- P08183
- Uniprot Name
- Multidrug resistance protein 1
- Molecular Weight
- 141477.255 Da
References
- Wu SJ, Robinson JR: Transport of human growth hormone across Caco-2 cells with novel delivery agents: evidence for P-glycoprotein involvement. J Control Release. 1999 Nov 1;62(1-2):171-7. doi: 10.1016/s0168-3659(99)00035-8. [Article]
Drug created at December 15, 2020 18:15 / Updated at February 10, 2022 08:54