Identification
- Summary
Emapalumab is an interferon gamma blocking antibody used to treat primary hemophagocytic lymphohistiocytosis.
- Brand Names
- Gamifant
- Generic Name
- Emapalumab
- DrugBank Accession Number
- DB14724
- Background
Emapalumab, also known as NI-0501, is a fully human monoclonal antibody that targets interferon gamma. Emapalumab development was sponsored by NovImmune SA, further developed by Sobi and FDA approved on November 20, 2018.1,5 The approval of emapalumab was followed by the designation of orphan drug, priority review and breakthrough therapy.5 As well, emapalumab was given the status of PRIME by the EMA.7
- Type
- Biotech
- Groups
- Approved, Investigational
- Biologic Classification
- Protein Based Therapies
Monoclonal antibody (mAb) - Protein Chemical Formula
- C6430H9898N1718O2038S46
- Protein Average Weight
- 154400.0 Da
- Sequences
- Not Available
- Synonyms
- Emapalumab
- Emapalumab-lzsg
- External IDs
- NI-0501
Pharmacology
- Indication
Emapalumab is indicated for the treatment of pediatric and adult patients with primary hemophagocytic lymphohistiocytosis (HLH) with refractory, recurrent or progressive disease or intolerance to conventional HLH therapy.5
The HLH condition is a hyperinflammatory status characterized by the overwhelming activation of normal T lymphocytes and macrophages which can lead to disturbances in the hematology profile and even death. As part of the condition profile, there have been reports proving a massive overexpression of interferon-gamma which is thought to drive the immune hyperactivation leading to organ failure.1 This condition is usually developed and present the symptomatic profile within the first months or years of life. These symptoms consist of fever, enlarged liver or spleen and a lower number of blood cells.5
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 Progressive, refractory, primary intolerance with conventional therapy, recurrent hemophagocytic lymphohistiocytosis •••••••••••• •••••• ••••••••• ••••••••• - Contraindications & Blackbox Warnings
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In phase 2/3 clinical trials, emapalumab administered concomitantly with dexamethasone reported an overall response in 63% of the patients. The overall response was defined as achievement of a complete or partial response or HLH improvement.6 In this trial and as a proof of interferon-gamma neutralization, there was registered a sharp decrease in serum CXCL9 and to avoid QT prolongation in the presence of low doses of emapalumab.8
- Mechanism of action
Emapalumab acts by binding and neutralizing interferon-gamma.1 The specific interaction between emapalumab and interferon-gamma produces an inhibition in the interaction between interferon-gamma and its cognate receptor on T-cells which produces the neutralizing activity.7 It is important to consider that emapalumab inhibits both free and IFNGR1-bound interferon-gamma as well as the interaction with IFNGR1 and IFNGR2 at the cell surface.3
HLH is an immune dysregulation syndrome in which several cytokines are involved but it has been reported that interferon-gamma plays a pivotal role in the development of this disease as studies have shown a vast increase in the interferon-gamma levels in HLH patients.2
Target Actions Organism AInterferon gamma neutralizerHumans - Absorption
In clinical pharmacokinetic studies, a dose of 1 mg/kg of emapalumab was administered which generated a peak concentration at steady state of 44 mcg/ml and a median steady-state concentration of 25 mcg/ml. The serum concentration of emapalumab increases proportionally between a dose of 1-3 mg/kg and the steady-state is attained by the 7th infusion.Label
- Volume of distribution
The central and peripheral volume of distribution of emapalumab are 4.2 and 5.6 L, respectively.Label
- Protein binding
Monoclonal antibodies are usually not required to have protein binding studies.Label
- Metabolism
Monoclonal antibodies are thought to be internalized in endothelial cells bound to Fc receptor and rescued from metabolism by recycling. Later, they are degraded in the reticuloendothelial system to small peptides and amino acids which can be used for de-novo protein synthesis.4
- Route of elimination
Emapalumab presents a target-mediated clearance that is dependent on interferon-gamma production.Label
- Half-life
Emapalumab elimination half-life is of approximately 22 days in healthy subjects and it ranges between 2.5-18.9 in HLH patients.Label
- Clearance
Emapalumab clearance is reported to be 0.007 L/h in healthy subjects. This clearance rate can vary in HLH patients depending on the production of interferon-gamma.Label
- Adverse Effects
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There are no reported effects in male or female reproductive organs after an 8- or 13-week repeat-dose toxicity study in animals.Label
- 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 softwareAbatacept The risk or severity of adverse effects can be increased when Abatacept is combined with Emapalumab. Abciximab The risk or severity of adverse effects can be increased when Abciximab is combined with Emapalumab. Abemaciclib The metabolism of Abemaciclib can be increased when combined with Emapalumab. Abrocitinib The metabolism of Abrocitinib can be increased when combined with Emapalumab. Acalabrutinib The metabolism of Acalabrutinib can be increased when combined with Emapalumab. - 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.- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Gamifant Injection 100 mg/4mL Intravenous SWEDISH ORPHAN BIOVITRUM AB (PUBL) 2023-06-07 Not applicable US 
Gamifant Injection 50 mg/10mL Intravenous NovImmune SA 2018-11-20 2021-11-30 US Gamifant Injection 10 mg/2mL Intravenous SWEDISH ORPHAN BIOVITRUM AB (PUBL) 2019-05-17 Not applicable US Gamifant Injection 500 mg/20mL Intravenous SWEDISH ORPHAN BIOVITRUM AB (PUBL) 2023-06-07 Not applicable US Gamifant Injection 50 mg/2mL Intravenous SWEDISH ORPHAN BIOVITRUM AB (PUBL) 2023-06-07 Not applicable US
Categories
- ATC Codes
- L04AA39 — Emapalumab
- Drug Categories
- Agents reducing cytokine levels
- Amino Acids, Peptides, and Proteins
- Antibodies
- Antibodies, Monoclonal
- Antineoplastic and Immunomodulating Agents
- Blood Proteins
- Globulins
- Immunoglobulins
- Immunoproteins
- Immunosuppressive Agents
- Interferon gamma Antagonists
- Interferon gamma Blocker
- Interferon-gamma
- Lymphohistiocytosis, Hemophagocytic
- Proteins
- Selective Immunosuppressants
- Serum Globulins
- 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
Chemical Identifiers
- UNII
- 3S252O2Z4X
- CAS number
- 1709815-23-5
References
- General References
- Kaplon H, Reichert JM: Antibodies to watch in 2018. MAbs. 2018 Feb/Mar;10(2):183-203. doi: 10.1080/19420862.2018.1415671. Epub 2018 Jan 16. [Article]
- Avau A, Matthys P: Therapeutic Potential of Interferon-gamma and Its Antagonists in Autoinflammation: Lessons from Murine Models of Systemic Juvenile Idiopathic Arthritis and Macrophage Activation Syndrome. Pharmaceuticals (Basel). 2015 Nov 25;8(4):793-815. doi: 10.3390/ph8040793. [Article]
- Zuber B, Rudstrom K, Ehrnfelt C, Ahlborg N: Epitope Mapping of Neutralizing Monoclonal Antibodies to Human Interferon-gamma Using Human-Bovine Interferon-gamma Chimeras. J Interferon Cytokine Res. 2016 Sep;36(9):542-51. doi: 10.1089/jir.2016.0017. Epub 2016 Jun 23. [Article]
- Tabrizi MA, Tseng CM, Roskos LK: Elimination mechanisms of therapeutic monoclonal antibodies. Drug Discov Today. 2006 Jan;11(1-2):81-8. doi: 10.1016/S1359-6446(05)03638-X. [Article]
- FDA news [Link]
- Clinical trials [Link]
- NHS [Link]
- American Society of Hematology [Link]
- External Links
- 2104603
- Wikipedia
- Emapalumab
- FDA label
- Download (521 KB)
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 4 Active Not Recruiting Treatment Primary Hemophagocytic Lymphohistiocytosis 1 3 Completed Treatment Primary Hemophagocytic Lymphohistiocytosis 1 3 Recruiting Treatment AOSD / Macrophage Activation Syndrome / MAS / Secondary Hemophagocytic Lymphohistiocytosis / SJIA / Still's Disease / Systemic Lupus Erythematosus 1 2 Completed Treatment Adult Onset Still's Disease / Hemophagocytic Lymphohistiocytosis / Juvenile Idiopathic Arthritis (JIA) / Macrophage Activation Syndrome 1 2 Recruiting Treatment Autoimmune Lymphoproliferative Syndrome (ALPS) / Immune System Diseases / Primary Immune Regulatory Disorder 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Injection Intravenous 10 mg/2mL Injection Intravenous 100 mg/4mL Injection Intravenous 100 mg/20mL Injection Intravenous 250 mg/10mL Injection Intravenous 50 mg/2mL Injection Intravenous 50 mg/10mL Injection Intravenous 500 mg/20mL - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 78 ºC Ji-Hee, et al. Front Immunol, 7:394 (2016) boiling point (°C) Fab and Fc domains denaturates at 60 and 70 ºC respectively Arnoldus W. et al. (2000). Biophysical Journal. Vol 78. 394-404 water solubility 50 mg/ml Human IgG purified. Product Information isoelectric point 6.6 - 7.2 Jin, et al. Electrophoresis. Sep;23(19):3385-91. (2002).
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Neutralizer
- General Function
- Interferon-gamma receptor binding
- Specific Function
- Produced by lymphocytes activated by specific antigens or mitogens. IFN-gamma, in addition to having antiviral activity, has important immunoregulatory functions. It is a potent activator of macrop...
- Gene Name
- IFNG
- Uniprot ID
- P01579
- Uniprot Name
- Interferon gamma
- Molecular Weight
- 19348.165 Da
References
- Kaplon H, Reichert JM: Antibodies to watch in 2018. MAbs. 2018 Feb/Mar;10(2):183-203. doi: 10.1080/19420862.2018.1415671. Epub 2018 Jan 16. [Article]
Drug created at November 29, 2018 17:57 / Updated at March 18, 2023 08:02