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 with congenital or acquired generalized 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 congenital or acquired lipodystrophy. Affecting less than 500 people worldwide, lipodystrophy is characterized by a lack of adipose tissue, fat deposition in the muscles and liver, and metabolic complications such as hypertriglyceridemia, insulin resistance, diabetes mellitus, and fatty liver disease. These metabolic abnormalities are often aggravated by excessive food intake, which is further aggravated by leptin deficiency, a protein secreted by adipose tissue. 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. It is administered as a once daily subcutaneous injection. On Feb. 24, 2014, Metreleptin was approved by the FDA for the treatment of complications of leptin deficiency, in addition to diet, in patients with congenital generalized or acquired generalized lipodystrophy. Metreleptin is marketed under the brand Myalept® by Aegerion Pharmaceuticals, Inc.
- 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 Format- 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.6
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- Contraindications & Blackbox Warnings
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In patients with leptin deficiency, clinical trials demonstrated that exogenous leptin administration results in weight loss, reduction in mean HbA1c and fasting glucose levels, reduced blood insulin, and reduced triglyceride levels leading to improved insulin sensitivity and reductions in food intake.
- Mechanism of action
Metreleptin functions by binding to and activating the human leptin receptor (ObR), which belongs to the Class I cytokine family of receptors that signals through the JAK/STAT transduction pathway.
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.
- 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.
- 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.
- Route of elimination
Nonclinical data indicate renal clearance is the major route of metreleptin elimination, with no apparent contribution of systemic metabolism or degradation.
- Half-life
3.8 to 4.7 hours
- Clearance
The clearance of metreleptin is expected to be delayed in the presence of leptin antibodies.
- Adverse Effects
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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. 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. 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. 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.
- 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. Acetaminophen The metabolism of Acetaminophen can be increased when combined with Metreleptin. Acetohexamide Metreleptin may increase the hypoglycemic activities of Acetohexamide. Adagrasib The metabolism of Adagrasib can be increased when combined with Metreleptin. Albendazole The metabolism of Albendazole can be increased when combined with Metreleptin. Alectinib The metabolism of Alectinib can be increased when combined with Metreleptin. 
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- 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 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 Myalept Injection, powder, lyophilized, for solution 11.3 mg/2.2mL Subcutaneous Amylin Pharmaceuticals, Llc. 2014-05-22 2018-03-31 US Myalepta Injection, powder, for solution 11.3 mg Subcutaneous Amryt Pharmaceuticals DAC 2020-12-15 Not applicable EU 
Myalepta Injection, powder, for solution 3 mg Subcutaneous Amryt Pharmaceuticals DAC 2020-12-15 Not applicable EU Myalepta Injection, powder, for solution 11.3 mg Subcutaneous Amryt Pharmaceuticals DAC 2020-12-15 Not applicable EU Myalepta Injection, powder, for solution 5.8 mg Subcutaneous Amryt Pharmaceuticals DAC 2020-12-15 Not applicable EU Myalepta Injection, powder, for solution 3 mg Subcutaneous Amryt Pharmaceuticals DAC 2020-12-15 Not applicable EU Myalepta Injection, powder, for solution 5.8 mg Subcutaneous Amryt Pharmaceuticals DAC 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]
- FDA Approved Drug Products: Myalept (metreleptin) for subcutaneous injection [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
Phase Status Purpose Conditions Count 4 Recruiting Treatment Generalized Lipodystrophy 1 3 Recruiting Treatment Diabetes / Hyperlipidemias / Lipodystrophies 1 3 Recruiting Treatment Partial Lipodystrophy 1 2 Active Not Recruiting Treatment Diabetes / Hyperlipidemias / Lipodystrophies 1 2 Active Not Recruiting Treatment Severe Insulin Resistance 1 2 Completed Treatment (NAFLD) / Lipodystrophy, Familial Partial / Non Alcoholic Steatohepatitis (NASH) 1 2 Completed Treatment Amenorrhea 1 2 Completed Treatment Diabetes / Obesity / Syndrome, Metabolic 2 2 Completed Treatment Fatty Liver, Non-alcoholic Fatty Liver Disease, NAFLD 1 2 Completed Treatment Fatty Liver, Non-alcoholic Fatty Liver Disease, NAFLD / Lipodystrophies / Non Alcoholic Steatohepatitis (NASH) 1
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 - 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
- Transmembrane signaling receptor activity
- Specific Function
- Receptor for obesity factor (leptin). On ligand binding, mediates signaling through JAK2/STAT3. Involved in the regulation of fat metabolism and, in a hematopoietic pathway, required for normal lym...
- 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]
Drug created at April 29, 2015 20:39 / Updated at March 29, 2022 04:50