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Identification
- Summary
Inebilizumab is a humanized anti-CD19 cytolytic monoclonal antibody for B-cell depletion in autoimmune conditions. Currently approved only for neuromyelitis optica spectrum disorder (NMOSD).
- Brand Names
- Uplizna 3 Vial Kit
- Generic Name
- Inebilizumab
- DrugBank Accession Number
- DB12530
- Background
Inappropriate growth of or self-directed antibody production by B-cells is the etiological underpinning of a variety of conditions, including the multiple sclerosis-like neurological condition neuromyelitis optica spectrum disorder (NMOSD).2,3 Inebilizumab is a humanized afucosylated monoclonal IgG1 antibody directed against the broadly expressed B-cell surface antigen CD19. Inebilizumab is cytolytic, resulting in B-cell depletion and offering therapeutic benefit to patients suffering from NMOSD. Compared to the anti-CD20 antibody rituximab, which is also used to treat NMOSD, inebilizumab has broader specificity.1,4,5,6,7,8
Inebilizumab was granted FDA approval on June 11, 2020, for the treatment of anti-aquaporin 4 positive NMOSD patients.9 Given its mechanism of action and good safety profile, it may prove useful in the treatment of other conditions linked to autoimmune antibody production or B-cell malignancies.1,6 On January 16, 2024, Iinebilizumab also received Health Canada approval for the same indication.11
- Type
- Biotech
- Groups
- Approved, Investigational
- Biologic Classification
- Protein Based Therapies
Monoclonal antibody (mAb) - Protein Chemical Formula
- Not Available
- Protein Average Weight
- 149000.0 Da (approximate)
- Sequences
- Not Available
- Synonyms
- Inebilizumab
- inebilizumab-cdon
- External IDs
- MEDI 551
- MEDI-551
- MEDI551
Pharmacology
- Indication
Inebilizumab is indicated for the treatment of aquaporin-4 (AQP4) immunoglobulin-positive (AQP4-IgG) neuromyelitis optica spectrum disorder (NMOSD) in adult patients.9
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Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Treatment of Neuromyelitis optica spectrum disorder •••••••••••• ••••• •••••••••••••• • •••••••• •••••••• ••••••••• Treatment of Neuromyelitis optica spectrum disorders •••••••••••• ••••• •••••••••••••• • •••••••• •••••••• ••••••••• - Contraindications & Blackbox Warnings
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Inebilizumab is a CD19-directed monoclonal antibody that results in immunosuppression through B-cell depletion with sufficient efficacy to allow a six-month dosing schedule.1,4,5,9 Due to this mechanism of action, patients undergoing inebilizumab treatment may be at higher risk of infections and should be monitored for active infections and immunoglobulin levels while undergoing treatment; vaccination is not recommended during inebilizumab treatment. Also, there is a risk of severe infusion reactions. Animal data suggests the possibility of fetal harm with inebilizumab and therefore, effective contraception during and for six months following inebilizumab treatment is recommended.9
- Mechanism of action
Neuromyelitis optica spectrum disorder (NMOSD), formerly referred to as Devic's disease, is an antibody-mediated autoimmune condition resulting in astroglial cell death, demyelination, and central nervous system (CNS) inflammation.2,3 The presence of anti-aquaporin 4 immunoglobulin (AQP4-IgG) is the most frequent biomarker, although AQP4-IgG negative, anti-myelin oligodendrocyte glycoprotein (anti-MOG) positive, variants with similar presentation also exist.2,3 The theoretical origin of symptoms is through AQP4-IgG-mediated astrocyte cytotoxicity and subsequent infiltration of neutrophils, eosinophils, and macrophages, leading to inflammatory-mediated oligodendrocyte damage and myelin sheath loss.3 In general, this manifests as optic neuritis and transverse myelitis with occasional involvement of the diencephalic, brainstem, and cerebral hemisphere.6
CD19 is a B-cell surface antigen expressed on most B-cells,1 including the expanded population of CD27high CD38high CD180- CD19+ plasmablasts that are the origin of astrocytic AQP4-IgG in most NMOSD patients.2,3 Inebilizumab binds to CD19 and, through one of several potential mechanisms, results in cell death.1,4,5,9 Destruction of the specific AQP4-IgG-producing plasmablasts results in lower amounts of AQP4-IgG in the CNS and therefore slows neuronal damage and improves patient outcomes.6
Target Actions Organism AB-lymphocyte antigen CD19 binderHumans - Absorption
Inebilizumab is given intravenously and hence is immediately exposed to the systemic circulation. The mean reported Cmax following second dose 300 mg administration was 108 μg/mL, and the cumulative AUC following 26 weeks of treatment with two IV administrations was 2980 μg*d/mL.9
In a clinical trial investigating the use of inebilizumab in relapsing multiple sclerosis, the mean Cmax corresponding to 30, 100, and 600 mg of inebilizumab was 17.9, 43.1, and 248.0 μg/mL and the AUC0-∞ was 440, 1150, and 6950 μg*d/mL.7 In another trial for patients with systemic sclerosis, the mean Cmax varied between 2.7 and 227.0 μg/mL and the AUC0-∞ varied between 16.1 and 2890.0 μg*d/mL for doses between 0.1 and 10.0 mg/kg.8
- Volume of distribution
Inebilizumab has an estimated central volume of distribution of 2.95L and a peripheral volume of distribution of 2.57L.9 The steady-state volume of distribution in patients administered with a range of doses between 0.1 and 10.0 mg/kg ranged from 53.7 to 71.7 mL/kg.8
- Protein binding
Not Available
- Metabolism
Inebilizumab is a monoclonal antibody and is hence likely degraded through proteolysis.9
- Route of elimination
Not Available
- Half-life
Inebilizumab exhibits biphasic pharmacokinetics with a mean terminal half-life of 18 days.9 The terminal half-life reported in phase I studies varied by dose but was typically close to 18 days, with a range of 6.8 to 18.7 days.7,8
- Clearance
Inebilizumab has an estimated systemic clearance of 0.19 L/day.9 In phase I studies, the reported clearance varied between 139-180 mL/day in one study,7 and 3.5-6.2 mL/kg/day in another,8 depending on the dose.
- Adverse Effects
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Toxicity information regarding inebilizumab is not readily available. Patients experiencing an overdose are at an increased risk of severe adverse effects such as severe infusion reactions, infections, and arthralgia. Symptomatic and supportive measures are recommended.
- 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 infection can be increased when Abatacept is combined with Inebilizumab. Abciximab The risk or severity of adverse effects can be increased when Abciximab is combined with Inebilizumab. Adalimumab The risk or severity of infection can be increased when Adalimumab is combined with Inebilizumab. Adenovirus type 7 vaccine live The risk or severity of infection can be increased when Adenovirus type 7 vaccine live is combined with Inebilizumab. Aducanumab The risk or severity of adverse effects can be increased when Aducanumab is combined with Inebilizumab. - 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 Uplizna Injection, solution, concentrate 100 mg Intravenous Horizon Therapeutics Ireland Dac 2022-05-24 Not applicable EU 
Uplizna Injection 10 mg/1mL Intravenous Viela Bio, Inc. 2020-06-11 Not applicable US 
Uplizna Solution 10 mg / mL Intravenous Horizon Therapeutics Ireland Dac Not applicable Not applicable Canada 
Uplizna Injection 10 mg/1mL Intravenous Horizon Therapeutics USA, Inc. 2020-06-11 Not applicable US
Categories
- ATC Codes
- L04AG10 — Inebilizumab
- Drug Categories
- Amino Acids, Peptides, and Proteins
- Antibodies
- Antibodies, Monoclonal
- Antibodies, Monoclonal, Humanized
- Antineoplastic and Immunomodulating Agents
- Blood Proteins
- CD19 Directed Cytolytic Antibodies
- CD19-directed Cytolytic Antibody
- Globulins
- Immunoglobulins
- Immunoproteins
- Immunosuppressive Agents
- 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 and other mammals
Chemical Identifiers
- UNII
- 74T7185BMM
- CAS number
- 1299440-37-1
References
- Synthesis Reference
Herbst R, Wang Y, Gallagher S, Mittereder N, Kuta E, Damschroder M, Woods R, Rowe DC, Cheng L, Cook K, Evans K, Sims GP, Pfarr DS, Bowen MA, Dall'Acqua W, Shlomchik M, Tedder TF, Kiener P, Jallal B, Wu H, Coyle AJ: B-cell depletion in vitro and in vivo with an afucosylated anti-CD19 antibody. J Pharmacol Exp Ther. 2010 Oct;335(1):213-22. doi: 10.1124/jpet.110.168062. Epub 2010 Jul 6.
- General References
- Herbst R, Wang Y, Gallagher S, Mittereder N, Kuta E, Damschroder M, Woods R, Rowe DC, Cheng L, Cook K, Evans K, Sims GP, Pfarr DS, Bowen MA, Dall'Acqua W, Shlomchik M, Tedder TF, Kiener P, Jallal B, Wu H, Coyle AJ: B-cell depletion in vitro and in vivo with an afucosylated anti-CD19 antibody. J Pharmacol Exp Ther. 2010 Oct;335(1):213-22. doi: 10.1124/jpet.110.168062. Epub 2010 Jul 6. [Article]
- Weinshenker BG, Wingerchuk DM: Neuromyelitis Spectrum Disorders. Mayo Clin Proc. 2017 Apr;92(4):663-679. doi: 10.1016/j.mayocp.2016.12.014. [Article]
- Wu Y, Zhong L, Geng J: Neuromyelitis optica spectrum disorder: Pathogenesis, treatment, and experimental models. Mult Scler Relat Disord. 2019 Jan;27:412-418. doi: 10.1016/j.msard.2018.12.002. Epub 2018 Dec 3. [Article]
- Gallagher S, Turman S, Yusuf I, Akhgar A, Wu Y, Roskos LK, Herbst R, Wang Y: Pharmacological profile of MEDI-551, a novel anti-CD19 antibody, in human CD19 transgenic mice. Int Immunopharmacol. 2016 Jul;36:205-212. doi: 10.1016/j.intimp.2016.04.035. Epub 2016 May 7. [Article]
- Gallagher S, Yusuf I, McCaughtry TM, Turman S, Sun H, Kolbeck R, Herbst R, Wang Y: MEDI-551 Treatment Effectively Depletes B Cells and Reduces Serum Titers of Autoantibodies in Mice Transgenic for Sle1 and Human CD19. Arthritis Rheumatol. 2016 Apr;68(4):965-76. doi: 10.1002/art.39503. [Article]
- Cree BAC, Bennett JL, Kim HJ, Weinshenker BG, Pittock SJ, Wingerchuk DM, Fujihara K, Paul F, Cutter GR, Marignier R, Green AJ, Aktas O, Hartung HP, Lublin FD, Drappa J, Barron G, Madani S, Ratchford JN, She D, Cimbora D, Katz E: Inebilizumab for the treatment of neuromyelitis optica spectrum disorder (N-MOmentum): a double-blind, randomised placebo-controlled phase 2/3 trial. Lancet. 2019 Oct 12;394(10206):1352-1363. doi: 10.1016/S0140-6736(19)31817-3. Epub 2019 Sep 5. [Article]
- Agius MA, Klodowska-Duda G, Maciejowski M, Potemkowski A, Li J, Patra K, Wesley J, Madani S, Barron G, Katz E, Flor A: Safety and tolerability of inebilizumab (MEDI-551), an anti-CD19 monoclonal antibody, in patients with relapsing forms of multiple sclerosis: Results from a phase 1 randomised, placebo-controlled, escalating intravenous and subcutaneous dose study. Mult Scler. 2019 Feb;25(2):235-245. doi: 10.1177/1352458517740641. Epub 2017 Nov 16. [Article]
- Schiopu E, Chatterjee S, Hsu V, Flor A, Cimbora D, Patra K, Yao W, Li J, Streicher K, McKeever K, White B, Katz E, Drappa J, Sweeny S, Herbst R: Safety and tolerability of an anti-CD19 monoclonal antibody, MEDI-551, in subjects with systemic sclerosis: a phase I, randomized, placebo-controlled, escalating single-dose study. Arthritis Res Ther. 2016 Jun 7;18(1):131. doi: 10.1186/s13075-016-1021-2. [Article]
- FDA Approved Drug Products: Uplizna (inebilizumab-cdon) injection [Link]
- Health Canada Approved Drug Proucts: UPLIZNA (Inebilizumab) injection for intravenenous use [Link]
- Health Canada Approves UPLIZNA® (inebilizumab for injection) for the Treatment of Neuromyelitis Optica Spectrum Disorders (NMOSD) [Link]
- External Links
- PubChem Substance
- 347911342
- 2373951
- Wikipedia
- Inebilizumab
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 Not Yet Recruiting Not Available Neuromyelitis Optica Spectrum Disorders 1 somestatus stop reason just information to hide 4 Not Yet Recruiting Treatment Neuromyelitis Optica Spectrum Disorders 1 somestatus stop reason just information to hide 4 Recruiting Treatment Neuromyelitis Optica Spectrum Disorders 1 somestatus stop reason just information to hide 3 Active Not Recruiting Treatment Immunoglobulin G4 Related Sclerosing Disease 1 somestatus stop reason just information to hide 3 Active Not Recruiting Treatment Myasthenia Gravis 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Injection Intravenous 10 mg/1mL Injection, solution, concentrate Intravenous 100 mg Solution Intravenous 10 mg / mL - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
- Not Available
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Binder
- Curator comments
- Inebilizumab is an anti-CD19 antibody. Binding to CD19 results in B-cell cytotoxicity and depletion, which alleviates the autoimmune symptoms of NMOSD.
- General Function
- Functions as a coreceptor for the B-cell antigen receptor complex (BCR) on B-lymphocytes. Decreases the threshold for activation of downstream signaling pathways and for triggering B-cell responses to antigens (PubMed:1373518, PubMed:16672701, PubMed:2463100). Activates signaling pathways that lead to the activation of phosphatidylinositol 3-kinase and the mobilization of intracellular Ca(2+) stores (PubMed:12387743, PubMed:16672701, PubMed:9317126, PubMed:9382888). Is not required for early steps during B cell differentiation in the blood marrow (PubMed:9317126). Required for normal differentiation of B-1 cells (By similarity). Required for normal B cell differentiation and proliferation in response to antigen challenges (PubMed:1373518, PubMed:2463100). Required for normal levels of serum immunoglobulins, and for production of high-affinity antibodies in response to antigen challenge (PubMed:12387743, PubMed:16672701, PubMed:9317126)
- Specific Function
- Not Available
- Gene Name
- CD19
- Uniprot ID
- P15391
- Uniprot Name
- B-lymphocyte antigen CD19
- Molecular Weight
- 61127.985 Da
References
- Herbst R, Wang Y, Gallagher S, Mittereder N, Kuta E, Damschroder M, Woods R, Rowe DC, Cheng L, Cook K, Evans K, Sims GP, Pfarr DS, Bowen MA, Dall'Acqua W, Shlomchik M, Tedder TF, Kiener P, Jallal B, Wu H, Coyle AJ: B-cell depletion in vitro and in vivo with an afucosylated anti-CD19 antibody. J Pharmacol Exp Ther. 2010 Oct;335(1):213-22. doi: 10.1124/jpet.110.168062. Epub 2010 Jul 6. [Article]
- Gallagher S, Turman S, Yusuf I, Akhgar A, Wu Y, Roskos LK, Herbst R, Wang Y: Pharmacological profile of MEDI-551, a novel anti-CD19 antibody, in human CD19 transgenic mice. Int Immunopharmacol. 2016 Jul;36:205-212. doi: 10.1016/j.intimp.2016.04.035. Epub 2016 May 7. [Article]
- Gallagher S, Yusuf I, McCaughtry TM, Turman S, Sun H, Kolbeck R, Herbst R, Wang Y: MEDI-551 Treatment Effectively Depletes B Cells and Reduces Serum Titers of Autoantibodies in Mice Transgenic for Sle1 and Human CD19. Arthritis Rheumatol. 2016 Apr;68(4):965-76. doi: 10.1002/art.39503. [Article]
- FDA Approved Drug Products: Uplizna (inebilizumab-cdon) injection [Link]
Drug created at October 20, 2016 22:44 / Updated at February 01, 2024 01:51