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.

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 It is available as a once-weekly subcutaneous injection.5

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
References:
  1. Health Canada Approved Drug Products: NGENLA (Somatrogon) subcutaneous injection [Link]
Download FASTA Format
Synonyms
  • Somatrogon
External IDs
  • MOD-4023

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

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Associated Conditions
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

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.
DrugInteraction
1,2-BenzodiazepineThe metabolism of 1,2-Benzodiazepine can be increased when combined with Somatrogon.
AbemaciclibThe metabolism of Abemaciclib can be increased when combined with Somatrogon.
AbirateroneThe metabolism of Abiraterone can be increased when combined with Somatrogon.
AcalabrutinibThe metabolism of Acalabrutinib can be increased when combined with Somatrogon.
AcarboseThe therapeutic efficacy of Acarbose can be decreased when used in combination with Somatrogon.
AcenocoumarolThe metabolism of Acenocoumarol can be increased when combined with Somatrogon.
AcetaminophenThe metabolism of Acetaminophen can be increased when combined with Somatrogon.
AcetohexamideThe therapeutic efficacy of Acetohexamide can be decreased when used in combination with Somatrogon.
AcyclovirThe metabolism of Acyclovir can be increased when combined with Somatrogon.
AgomelatineThe metabolism of Agomelatine can be increased when combined with Somatrogon.
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Food Interactions
No interactions found.

Products

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Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
NgenlaInjection, solution60 mg/1.2mlSubcutaneousPfizer Europe Ma Eeig2022-05-04Not applicableEU flag
NgenlaSolution20 mg / mLSubcutaneousPfizer Canada Ulc2022-02-22Not applicableCanada flag
NgenlaInjection, solution24 mg/1.2mlSubcutaneousPfizer Europe Ma Eeig2022-05-04Not applicableEU flag
NgenlaSolution50 mg / mLSubcutaneousPfizer Canada Ulc2022-02-22Not applicableCanada flag

Categories

Drug Categories
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
Not Available

Chemical Identifiers

UNII
6D848RA61B
CAS number
1663481-09-1

References

General References
  1. 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]
  2. Bidlingmaier M, Strasburger CJ: Growth hormone. Handb Exp Pharmacol. 2010;(195):187-200. doi: 10.1007/978-3-540-79088-4_8. [Article]
  3. 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]
  4. Pfizer: HEALTH CANADA APPROVES NGENLA (SOMATROGON) INJECTION FOR PEDIATRIC GROWTH HORMONE DEFICIENCY [Link]
  5. OPKO: About Somatrogon [Link]
  6. Health Canada Approved Drug Products: NGENLA (Somatrogon) subcutaneous injection [Link]
Not Available

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3Active Not RecruitingTreatmentChildhood-onset Growth Hormone Deficiency1
3CompletedOtherHuman Growth Hormone Deficiency2
3TerminatedTreatmentAdult Onset Growth Hormone Deficiency1
2Active Not RecruitingTreatmentHuman Growth Hormone Deficiency1
2CompletedTreatmentAdult Onset Growth Hormone Deficiency1
2CompletedTreatmentChildhood-onset Growth Hormone Deficiency1
1CompletedOtherHealthy Male Volunteers1
1CompletedOtherHuman Growth Hormone Deficiency1
1CompletedTreatmentHealthy Subjects (HS)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
Injection, solutionSubcutaneous24 mg/1.2ml
Injection, solutionSubcutaneous60 mg/1.2ml
SolutionSubcutaneous20 mg / mL
SolutionSubcutaneous50 mg / mL
Prices
Not Available
Patents
Not Available

Properties

State
Liquid
Experimental Properties
Not Available

Drug created at May 20, 2019 14:38 / Updated at December 07, 2021 13:41