Somatrogon
Identification
- Summary
Somatrogon is a long-acting recombinant human growth hormone used as the long-term treatment of pediatric patients who have growth failure due to growth hormone deficiency.
- Brand Names
- Ngenla
- Generic Name
- Somatrogon
- DrugBank Accession Number
- DB14960
- Background
Somatrogon is a long-acting recombinant human growth hormone. Growth hormone is a peptide hormone secreted by the pituitary gland that plays a crucial role in promoting longitudinal growth during childhood and adolescence and regulating metabolic function in adulthood.2 Recombinant growth hormone therapy for growth hormone deficiency and other conditions has been available since 1985, with daily administration being the standard treatment for many years. More recently, longer-acting forms of growth hormone were developed to improve patient adherence and thus, improve the therapeutic efficacy of treatment.1 Somatrogon was produced in Chinese Hamster Ovary (CHO) cells using recombinant DNA technology. It is a chimeric product generated by fusing three copies of the C-terminal peptide (CTP), or 28 carboxy-terminal residues, from the beta chain of human chorionic gonadotropin (hCG) to the N-terminus and C-terminus of human growth hormone.2,6 The glycosylation and the presence of CTPs in the protein sequence prolongs the half-life of somatrogon and allows its once-weekly dosing.6
In October 2021, Health Canada approved somatrogon under the market name NGENLA as the long-term treatment of pediatric patients who have growth failure due to an inadequate secretion of endogenous growth hormone caused by growth hormone deficiency, marking Canada as the first country to approve this drug.4 In June 2023, the FDA approved the use of somatrogon also for the treatment of pediatric growth hormone deficiency.7,8 Somatrogon is available as a once-weekly subcutaneous injection.5,7
- Type
- Biotech
- Groups
- Approved
- Biologic Classification
- Protein Based Therapies
Hormones - Protein Chemical Formula
- C1359H2125N361O420S7
- Protein Average Weight
- 30465.1 Da (Aglycosylated)
- Sequences
>Somatrogon amino acid sequence SSSSKAPPPSLPSPSRLPGPSDTPILPQFPTIPLSRLFDNAMLRAHRLHQLAFDTYQEFE EAYIPKEQKYSFLQNPQTSLCFSESIPTPSNREETQQKSNLELLRISLLLIQSWLEPVQF LRSVFANSLVYGASDSNVYDLLKDLEEGIQTLMGRLEDGSPRTGQIFKQTYSKFDTNSHN DDALLKNYGLLYCFRKDMDKVETFLRIVQCRSVEGSCGFSSSSKAPPPSLPSPSRLPGPS DTPILPQSSSSKAPPPSLPSPSRLPGPSDTPILPQ
Download FASTA FormatReferences:
- Health Canada Approved Drug Products: NGENLA (Somatrogon) subcutaneous injection [Link]
- Synonyms
- 118-145-GONADOTROPIN, CHORIONIC (HUMAN .BETA.-SUBUNIT) FUSION PROTEIN WITH SOMATOTROPIN (HUMAN) FUSION PROTEIN WITH 118-145-CHORIONIC GONADOTROPIN (HUMAN .BETA.-SUBUNIT) FUSION PROTEIN WITH 118-145-CHORIONIC GONADOTROPIN (HUMAN .BETA.-SUBUNIT)
- CTP-SOMATROPIN FUSION PROTEIN
- FUSION PROTEIN OF HUMAN CHORIOGONADOTROPIN SUBUNIT .BETA. (CG- .BETA.)-(118-145)-PEPTIDE (1-28) WITH HUMAN SOMATOTROPIN (GROWTH HORMONE, GH) (29-219) AND TWO TANDEM COPIES OF HUMAN CHORIOGONADOTROPIN SUBUNIT .BETA. (CG-.BETA.)-(118-145)- PEPTIDE (220-247
- HUMAN GROWTH HORMONE-CARBOXY-TERMINAL PEPTIDE (CTP) OF THE BETA CHAIN OF HUMAN CHORIONIC GONADOTROPIN FUSION PROTEIN
- MOD-423 hGH analogue
- Recombinant human growth hormone long acting (fused w beta chains of HCG)
- Somatrogon
- SOMATROPIN-CTP FUSION PROTEIN
- External IDs
- MOD 4023
- MOD-4023
- MOD4023
Pharmacology
- Indication
Somatrogon is indicated for the long-term treatment of pediatric patients who have growth failure due to an inadequate secretion of endogenous growth hormone (growth hormone deficiency).6,7
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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
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- Pharmacodynamics
Somatrogon mimics the physiological actions of endogenous growth hormone, such as cell proliferation, metabolism, and growth. It was also shown to increase the serum concentration of insulin-like growth factor (IGF-1).6
- Mechanism of action
Growth hormone is a key hormone that promotes body growth and regulates carbohydrate, protein and lipid metabolism.3 Somatrogon is a hormone replacement therapy that aims to restore deficient levels of growth hormone (GH). Like endogenous growth hormone, somatrogon binds to the GH receptor, which leads to the binding of JAK2 to GH receptor and activation of JAK2. Activation of JAK2 and phosphorylation of both JAK2 and GHR initiates the recruits various signalling proteins and facilitates multiple signalling pathways responsible for growth and metabolism.3 One of the activated signalling pathways is the STAT5b signalling pathway, which is critical for the effect of GH on body height.6
Target Actions Organism AGrowth hormone receptor binderHumans - Absorption
Following subcutaneous administration of 0.66 mg/kg/wk in pediatric patients with growth hormone deficiency, Cmax of somatrogon was 690 ng/mL. Tmax was 8 hours and the AUC was 21800 ng x h/mL. Over the dose range of 0.25-0.66 mg/kg/week, somatrogon exposure increased in a dose-proportional manner.6
- Volume of distribution
Following subcutaneous administration of 0.66 mg/kg/wk in pediatric patients with growth hormone deficiency, the apparent central volume of distribution (Vc) was 0.812 L/kg and the apparent peripheral volume of distribution (Vt) was 0.169 L/kg. Somatrogon does not accumulate after once-weekly administration.6
- Protein binding
There is no information available.
- Metabolism
Somatrogon is expected to undergo protein catabolism, with subsequent reclamation of the amino acids and return to the systemic circulation.6
- Route of elimination
There is no information available.
- Half-life
Following subcutaneous administration of 0.66 mg/kg/wk in pediatric patients with growth hormone deficiency, the half-life was 28.3 hours. Somatrogon was detected in the circulation for about 6 days after the last dose.6
- Clearance
Following subcutaneous administration of 0.66 mg/kg/wk in pediatric patients with growth hormone deficiency, the clearance was 0.0336 L/h/kg.6
- Adverse Effects
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- Toxicity
Subcutaneous doses of somatrogon higher than 0.66 mg/kg per week have not been studied. Based on existing clinical data of other growth hormone products, short-term overdosage from somatrogon could lead initially to hypoglycemia and subsequently to hyperglycemia. Long-term overdosage could result in signs and symptoms of gigantism or acromegaly consistent with the effects of excess growth hormone. Overdose with somatrogon should be treated with general supportive measures.6
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- 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 software1,2-Benzodiazepine The metabolism of 1,2-Benzodiazepine can be increased when combined with Somatrogon. Abemaciclib The metabolism of Abemaciclib can be increased when combined with Somatrogon. Abiraterone The metabolism of Abiraterone can be increased when combined with Somatrogon. Acalabrutinib The metabolism of Acalabrutinib can be increased when combined with Somatrogon. Acarbose The therapeutic efficacy of Acarbose can be decreased when used in combination with Somatrogon. - 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.
- International/Other Brands
- Ngenla (Pfizer, Inc.)
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Ngenla Solution 20 mg / mL Subcutaneous Pfizer Canada Ulc 2022-02-22 Not applicable Canada Ngenla Injection, solution 60 mg/1.2ml Subcutaneous Pfizer Europe Ma Eeig 2022-05-04 Not applicable EU Ngenla Injection, solution 24 mg/1.2mL Subcutaneous Pfizer Laboratories Div Pfizer Inc 2023-07-31 Not applicable US Ngenla Injection, solution 24 mg/1.2ml Subcutaneous Pfizer Europe Ma Eeig 2022-05-04 Not applicable EU Ngenla Solution 50 mg / mL Subcutaneous Pfizer Canada Ulc 2022-02-22 Not applicable Canada
Categories
- ATC Codes
- H01AC08 — Somatrogon
- Drug Categories
- Amino Acids, Peptides, and Proteins
- Anterior Pituitary Lobe Hormones and Analogues
- Growth Hormone
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Peptide Hormones
- Peptides
- Pituitary and Hypothalamic Hormones and Analogues
- Pituitary Hormones
- Pituitary Hormones, Anterior
- Recombinant Human Growth Hormone
- Somatropin and Somatropin Agonists
- Systemic Hormonal Preparations, Excl. Sex Hormones and Insulins
- Chemical TaxonomyProvided by Classyfire
- Description
- Not Available
- Kingdom
- Organic Compounds
- Super Class
- Organic Acids
- Class
- Carboxylic Acids and Derivatives
- Sub Class
- Amino Acids, Peptides, and Analogues
- Direct Parent
- Peptides
- Alternative Parents
- Not Available
- Substituents
- Not Available
- Molecular Framework
- Not Available
- External Descriptors
- Not Available
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 6D848RA61B
- CAS number
- 1663481-09-1
References
- General References
- Lal RA, Hoffman AR: Perspectives on long-acting growth hormone therapy in children and adults. Arch Endocrinol Metab. 2019 Nov-Dec;63(6):601-607. doi: 10.20945/2359-3997000000190. [Article]
- Bidlingmaier M, Strasburger CJ: Growth hormone. Handb Exp Pharmacol. 2010;(195):187-200. doi: 10.1007/978-3-540-79088-4_8. [Article]
- Carter-Su C, Schwartz J, Argetsinger LS: Growth hormone signaling pathways. Growth Horm IGF Res. 2016 Jun;28:11-5. doi: 10.1016/j.ghir.2015.09.002. Epub 2015 Sep 10. [Article]
- Pfizer: HEALTH CANADA APPROVES NGENLA (SOMATROGON) INJECTION FOR PEDIATRIC GROWTH HORMONE DEFICIENCY [Link]
- OPKO: About Somatrogon [Link]
- Health Canada Approved Drug Products: NGENLA (Somatrogon) subcutaneous injection [Link]
- FDA Approved Drug Products: NGENLA (somatrogon-ghla) injection for subcutaneous use (June 2023) [Link]
- BioSpace: FDA Approves Pfizer’s NGENLA, a Long-Acting Once-Weekly Treatment for Pediatric Growth Hormone Deficiency [Link]
- External Links
- 2644503
- Wikipedia
- Somatrogon
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 3 Active Not Recruiting Treatment Childhood-onset Growth Hormone Deficiency 1 3 Completed Other Human Growth Hormone Deficiency 2 3 Terminated Treatment Adult Onset Growth Hormone Deficiency 1 2 Completed Treatment Adult Onset Growth Hormone Deficiency 1 2 Completed Treatment Childhood-onset Growth Hormone Deficiency 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Injection, solution Subcutaneous 24 mg/1.2mL Injection, solution Subcutaneous 60 mg/1.2mL Solution Subcutaneous 20 mg / mL Solution Subcutaneous 50 mg / mL - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Liquid
- Experimental Properties
- Not Available
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Binder
- 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
Drug created at May 20, 2019 14:38 / Updated at September 30, 2023 19:52