Metreleptin
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Overview
- Description
- A medication used to treat a disorder in which the body is unable to use and store fat effectively.
- Description
- A medication used to treat a disorder in which the body is unable to use and store fat effectively.
- DrugBank ID
- DB09046
- Type
- Biotech
- Clinical Trials
- Phase 0
- 0
- Phase 1
- 4
- Phase 2
- 23
- Phase 3
- 4
- Phase 4
- 2
- Mechanism of Action
- Leptin receptorAgonist
- Leptin receptor
Identification
- Summary
Metreleptin is a leptin analogue used as an adjunct to diet as replacement therapy to treat the complications of leptin deficiency in patients various forms of lipodystrophy.
- Brand Names
- Myalept
- Generic Name
- Metreleptin
- DrugBank Accession Number
- DB09046
- Background
Metreleptin, a recombinant analog of the human hormone leptin, is an orphan drug used to treat complications of leptin deficiency in people with lipodystrophy. Lipodystrophies include a range of disorders characterized by the reduction, absence, or altered distribution of adipose tissue.6 Complications of lipodystrophy include metabolic abnormalities such as hypertriglyceridemia, insulin resistance, diabetes mellitus, and fatty liver disease.6 These metabolic abnormalities are often aggravated by excessive food intake, which is further aggravated by leptin deficiency, a protein secreted by adipose tissue.7 Administration of metreleptin results in improvement of metabolic symptoms including improvements in insulin resistance, reduced HbA1c and fasting glucose, reduced triglycerides, and reductions in food intake. Metreleptin is produced in E. coli and differs from native human leptin by the addition of a methionine residue at its amino terminus.7
In February 2014, metreleptin was approved by the FDA for the treatment of complications of leptin deficiency, as an adjunct to diet, in patients with congenital generalized or acquired generalized lipodystrophy.7 Metreleptin was approved by Health Canada in January 2024 for the same patient population, in addition to patients with partial lipodystrophy.8
- Type
- Biotech
- Groups
- Approved
- Biologic Classification
- Protein Based Therapies
Hormones - Protein Structure
- Protein Chemical Formula
- C714H1167N191O221S6
- Protein Average Weight
- 16155.4429 Da
- Sequences
>Peptide Sequence MVPIQKVQDDTKTLIKTIVTRINDISHTQSVSSKQKVTGLDFIPGLHPILTLSKMDQTLA VYQQILTSMPSRNVIQISNDLENLRDLLHVLAFSKSCHLPWASGLETLDSLGGVLEASGY STEVVALSRLQGSLQDMLWQLDLSPGC
Download FASTA FormatReferences:
- NIH Inxight Drugs: Metreleptin [Link]
- Synonyms
- Metreleptin
- Metreleptina
- Métréleptine
- Metreleptinum
- N-Methionylleptin
- r-metHuLeptin
- External IDs
- Leptin A-100
- Mettreleptin
Pharmacology
- Indication
Metreleptin is indicated as an adjunct to diet as replacement therapy to treat the complications of leptin deficiency in patients with congenital or acquired generalized lipodystrophy.7,8 In Canada, it is additionally approved for use in patients ≥12 years old with confirmed familial partial lipodystrophy or acquired partial lipodystrophy (Barraquer-Simons syndrome) and persistent significant metabolic disease for whom standard treatments have failed to achieve adequate metabolic control.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 Used as adjunct for symptomatic treatment of Leptin deficiency •••••••••••• •••••••• ••••••• ••••••••••••• ••••••••• Used as adjunct for symptomatic treatment of Leptin deficiency •••••••••••• •••••••••••••• •••••••• ••••••• ••••••••• Used as adjunct for symptomatic treatment of Leptin deficiency •••••••••••• •••••••• ••••••••••• ••••••••••••• ••••••••• Used as adjunct for symptomatic treatment of Leptin deficiency •••••••••••• •••••••••••••• •••••••••• ••••••••••• ••••••••• Used as adjunct for symptomatic treatment of Leptin deficiency •••••••••••• ••••••••• - 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
In clinical trials, patients treated with metreleptin showed improvements in insulin sensitivity and reductions in food intake, leading to subsequent reductions in HbA1c, fasting glucose, and fasting triglyceride values.7
- Mechanism of action
Metreleptin is an analog of an endogenous hormone, leptin, which is secreted by adipose tissue and helps to regulate satiety. Metreleptin mimics the physiological effects of leptin by binding to and activating the human leptin receptor (ObR).7,8
Target Actions Organism ALeptin receptor agonistHumans - Absorption
Peak serum leptin concentration (Cmax) occurred approximately 4.0 to 4.3 hours after subcutaneous administration of single doses ranging from 0.1 to 0.3 mg/kg in healthy subjects.7
- Volume of distribution
Following intravenous administration of metreleptin, leptin volume of distribution was approximately 4 to 5 times plasma volume; volumes (mean ± SD) were 370 ± 184 mL/kg, 398 ± 92 mL/kg, and 463 ± 116 mL/kg for 0.3, 1.0, and 3.0 mg/kg/day doses, respectively.7
- Protein binding
Not Available
- Metabolism
No formal metabolism studies have been conducted with metreleptin. Nonclinical data indicate renal clearance is the major route of metreleptin elimination, with no apparent contribution of systemic metabolism or degradation.7
- Route of elimination
Nonclinical data indicate renal clearance is the major route of metreleptin elimination, with no apparent contribution of systemic metabolism or degradation.7
- Half-life
Following subcutaneous administration of a single dose in healthy subjects, the half-life of metreleptin was 3.8 to 4.7 hours.7
- Clearance
The clearance of metreleptin is expected to be delayed in the presence of leptin antibodies.
- Adverse Effects
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- Toxicity
The most common adverse events reported for metreleptin use have been headache, hypoglycemia, weight loss, and abdominal pain. A boxed warning states that anti-metreleptin antibodies, serious infections, and worsening metabolic control have been reported in patients taking the drug, and that some patients with acquired generalized lipodystrophy taking metreleptin have developed T-cell lymphoma.7 Anti-metreleptin antibodies with neutralizing activity have been identified in patients treated with metreleptin which can lead to inhibition of endogenous leptin action and loss of drug efficacy.7 As part of a Risk Evaluation and Mitigation Strategy (REMS), the FDA has required healthcare providers to be trained in the use of metreleptin before prescribing it and to attest that patients for whom they prescribe metreleptin have a labeled indication for the drug.7 Metreleptin is classified as category C (no adequate studies in women) for use during pregnancy.
Two-year carcinogenicity studies in rodents have not been conducted with metreleptin. No proliferative or preneoplastic lesions were observed in mice or dogs following treatment up to six months. However, leptin is reported in the literature to promote cell proliferation in vitro and tumor progression in some mouse models of cancer. Metreleptin was not mutagenic in the Ames bacterial mutagenicity assay or clastogenic in an in vitro chromosomal aberration assay in Chinese hamster ovary cells and human peripheral blood lymphocytes. Metreleptin was not mutagenic or clastogenic in an in vivo mouse micronucleus assay. In a fertility study in mice, metreleptin had no adverse effects on mating, fertility, or early embryonic development at doses ranging between 7 and 15 times the maximum recommended clinical dose based on body surface area of a 20- and 60-kg patient, respectively.7
- 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 Metreleptin. Abemaciclib The metabolism of Abemaciclib can be increased when combined with Metreleptin. Abiraterone The metabolism of Abiraterone can be increased when combined with Metreleptin. Acalabrutinib The metabolism of Acalabrutinib can be increased when combined with Metreleptin. Acenocoumarol The metabolism of Acenocoumarol can be increased when combined with Metreleptin. - Food Interactions
- Take at the same time every day.
- Take with or without food.
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.
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Myalept Injection, powder, lyophilized, for solution 11.3 mg/2.2mL Subcutaneous Amylin Pharmaceuticals, Llc. 2014-05-22 2018-03-31 US Myalept Injection, powder, lyophilized, for solution 11.3 mg/2.2mL Subcutaneous Chiesi Italia s.p.a 2015-03-05 Not applicable US Myalept Injection, powder, lyophilized, for solution 11.3 mg/2.2mL Subcutaneous Catalent Pharma Solution, LLC 2015-03-05 2018-03-23 US Myalept Injection, powder, lyophilized, for solution 11.3 mg/2.2mL Subcutaneous Amryt Pharmaceuticals DAC 2015-03-05 Not applicable US Myalepta Injection, powder, for solution 3 mg Subcutaneous Chiesi Farmaceutici S.P.A. 2020-12-15 Not applicable EU
Categories
- ATC Codes
- A16AA07 — Metreleptin
- Drug Categories
- Adipokines
- Alimentary Tract and Metabolism
- Amino Acids and Derivatives
- Amino Acids, Peptides, and Proteins
- Analogs/Derivatives
- Biological Factors
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Intercellular Signaling Peptides and Proteins
- Leptin Analog
- Obesity, drug therapy
- Peptide Hormones
- Peptides
- Proteins
- 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
- TL60C27RLH
- CAS number
- 186018-45-1
References
- General References
- Paz-Filho G, Mastronardi CA, Licinio J: Leptin treatment: facts and expectations. Metabolism. 2015 Jan;64(1):146-56. doi: 10.1016/j.metabol.2014.07.014. Epub 2014 Aug 3. [Article]
- Tsoukas MA, Farr OM, Mantzoros CS: Leptin in congenital and HIV-associated lipodystrophy. Metabolism. 2015 Jan;64(1):47-59. doi: 10.1016/j.metabol.2014.07.017. Epub 2014 Aug 12. [Article]
- Farr OM, Fiorenza C, Papageorgiou P, Brinkoetter M, Ziemke F, Koo BB, Rojas R, Mantzoros CS: Leptin therapy alters appetite and neural responses to food stimuli in brain areas of leptin-sensitive subjects without altering brain structure. J Clin Endocrinol Metab. 2014 Dec;99(12):E2529-38. doi: 10.1210/jc.2014-2774. [Article]
- Rodriguez AJ, Neeman T, Giles AG, Mastronardi CA, Paz Filho G: Leptin replacement therapy for the treatment of non-HAART associated lipodystrophy syndromes: a meta-analysis into the effects of leptin on metabolic and hepatic endpoints. Arq Bras Endocrinol Metabol. 2014 Nov;58(8):783-97. Epub 2014 Nov 1. [Article]
- Moon HS, Huh JY, Dincer F, Schneider BE, Hasselgren PO, Mantzoros CS: Identification and saturable nature of signaling pathways induced by metreleptin in humans: comparative evaluation of in vivo, ex vivo, and in vitro administration. Diabetes. 2015 Mar;64(3):828-39. doi: 10.2337/db14-0625. Epub 2014 Sep 23. [Article]
- Mainieri F, Chiarelli F: Lipodystrophies in Children. Horm Res Paediatr. 2022;95(4):305-320. doi: 10.1159/000522620. Epub 2022 Feb 21. [Article]
- FDA Approved Drug Products: Myalept (metreleptin) for subcutaneous injection [Link]
- Health Canada Product Monograph: Myalepta (metreleptin) injection for subcutaneous administration [Link]
- External Links
- UniProt
- P41159
- KEGG Drug
- D05014
- PubChem Substance
- 347910398
- 1491625
- ChEMBL
- CHEMBL2107857
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Metreleptin
- FDA label
- Download (1.81 MB)
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample dataNot Available Active Not Recruiting Basic Science Obesity 1 somestatus stop reason just information to hide Not Available Available Not Available Lipodystrophy, Familial Partial 1 somestatus stop reason just information to hide Not Available Completed Not Available Congenital leptin deficiency 1 somestatus stop reason just information to hide Not Available Completed Treatment HIV Lipodystrophy Syndrome 1 somestatus stop reason just information to hide Not Available Completed Treatment Lipodystrophies 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Injection, powder, lyophilized, for solution Subcutaneous 11.3 mg/2.2mL Injection, powder, for solution Parenteral; Subcutaneous 11.3 MG Injection, powder, for solution Parenteral; Subcutaneous 3 MG Injection, powder, for solution Parenteral; Subcutaneous 5.8 MG Injection, powder, for solution Subcutaneous 11.3 mg Injection, powder, for solution Subcutaneous 3 mg Injection, powder, for solution Subcutaneous 5.8 mg Powder, for solution Subcutaneous 11.3 mg / vial Powder, for solution Subcutaneous 3 mg / vial Powder, for solution Subcutaneous 5.8 mg / vial - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US20070099836 No 2006-11-29 2026-11-29 US US8318666 No 2012-11-27 2031-05-09 US US20130190225 No 2012-11-05 2032-11-05 US US8470772 No 2013-06-25 2029-02-27 US
Properties
- State
- Solid
- Experimental Properties
- Not Available
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Agonist
- General Function
- Receptor for hormone LEP/leptin (Probable) (PubMed:22405007). On ligand binding, mediates LEP central and peripheral effects through the activation of different signaling pathways such as JAK2/STAT3 and MAPK cascade/FOS. In the hypothalamus, LEP acts as an appetite-regulating factor that induces a decrease in food intake and an increase in energy consumption by inducing anorexinogenic factors and suppressing orexigenic neuropeptides, also regulates bone mass and secretion of hypothalamo-pituitary-adrenal hormones (By similarity) (PubMed:9537324). In the periphery, increases basal metabolism, influences reproductive function, regulates pancreatic beta-cell function and insulin secretion, is pro-angiogenic and affects innate and adaptive immunity (PubMed:12504075, PubMed:25060689, PubMed:8805376). Control of energy homeostasis and melanocortin production (stimulation of POMC and full repression of AgRP transcription) is mediated by STAT3 signaling, whereas distinct signals regulate NPY and the control of fertility, growth and glucose homeostasis. Involved in the regulation of counter-regulatory response to hypoglycemia by inhibiting neurons of the parabrachial nucleus. Has a specific effect on T lymphocyte responses, differentially regulating the proliferation of naive and memory T -ells. Leptin increases Th1 and suppresses Th2 cytokine production (By similarity)
- Specific Function
- cytokine binding
- Gene Name
- LEPR
- Uniprot ID
- P48357
- Uniprot Name
- Leptin receptor
- Molecular Weight
- 132492.66 Da
References
- Moon HS, Huh JY, Dincer F, Schneider BE, Hasselgren PO, Mantzoros CS: Identification and saturable nature of signaling pathways induced by metreleptin in humans: comparative evaluation of in vivo, ex vivo, and in vitro administration. Diabetes. 2015 Mar;64(3):828-39. doi: 10.2337/db14-0625. Epub 2014 Sep 23. [Article]
- FDA Approved Drug Products: Myalept (metreleptin) for subcutaneous injection [Link]
Drug created at April 29, 2015 20:39 / Updated at April 04, 2024 19:07