Identification
- Summary
Sarilumab is a monoclonal antibody used to treat moderate to severe rheumatoid arthritis who have responded poorly or are intolerant of other DMARDs.
- Brand Names
- Kevzara
- Generic Name
- Sarilumab
- DrugBank Accession Number
- DB11767
- Background
Sarilumab is a fully human anti-IL-6R monoclonal IgG1 antibody that binds to both membrane bound and soluble interleukin 6 (IL-6) receptor forms, thus blocking the cis- and trans-inflammatory signalling cascades of IL-6 1. Sarilumab was developped by Sanofi and Regeneron Pharmaceuticals, Inc; it was US FDA-approved in May 2017 and followed by EU approval in June 2017 for the treatment of moderate to severe Rheumatoid Arthritis (RA) in combination with methotrexate 4. RA is a chronic inflammatory disease characterized by polyarthritis and its treatment has been challenged by the different response in every patient 3. Subcutaneous administration of Sarilumab has been shown to decrease acute-phase reactant levels and improve in clinical RA symptoms 2.
- Type
- Biotech
- Groups
- Approved, Investigational
- Biologic Classification
- Protein Based Therapies
Monoclonal antibody (mAb) - Protein Structure
- Protein Chemical Formula
- C6388H9918N1718O1998S44
- Protein Average Weight
- 150000.0 Da (143900 Da in absence of N-glycosylation in heavy chains (Asn296))
- Sequences
> Heavy chain EVQLVESGGGLVQPGRSLRLSCAASRFTFDDYAMHWVRQAPGKGLEWVSGISWNSGRIGY ADSVKGRFTISRDNAENSLFLQMNGLRAEDTALYYCAKGRDSFDIWGQGTMVTVSSASTK GPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYS LSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVF LFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYR VVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKN QVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGN VFSCSVMHEALHNHYTQKSLSLSPGK
>Light chain DIQMTQSPSSVSASVGDRVTITCRASQGISSWLAWYQQKPGKAPKLLIYGASSLESGVPS RFSGSGSGTDFTLTISSLQPEDFASYYCQQANSFPYTFGQGTKLEIKRTVAAPSVFIFPP SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT LSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
Download FASTA Format- Synonyms
- REGN88
- SAR153191
- Sarilumab
Pharmacology
- Indication
Indicated for modere to severe reactive RA in adult patients who are irresponsive, respond inadequately or present intolerance to disease-modifying anti-rheumatic drugs (DMARDs) or tumor necrosis factor (TNF) antagonists. It is indicated to be used in combination with methotrexate (MTX) or as a monotherapy when there is intolerance to MTX or MTX administration is inappropriate.
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- Contraindications & Blackbox Warnings
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Single-dose subcutaneous administration of Sarilumab produced a rapid reduction of CRP levels, leading to normal levels after two weeks of treatment. Peak reduction in the absolute neutrophile count was observed after 3 to 4 days of treatment followed by a recovery to baseline levels. It is observed a decrease in fibrinogen and serum amyloid A as well as an increase in hemoglobin and serum albumin.
- Mechanism of action
Sarilumab is a human recombinant IgG1 antibody that binds to both forms of interleukin 6 receptors (IL-6R), thus inhibiting the IL-6-mediated signaling. IL-6 is known to be a pleiotropic cytokine that activates immune cells (T and B cells), as well as hepatocytes for the release of acute phase proteins like CRP, serum amyloid A and fibrinogen which are biomarkers of RA activity. IL-6 is also found in synovial fluid and plays a major role in the pathological inflammation and joint destruction features of RA. Thus, it is used for the treatment of RA due to its ability to inhibit intra-articular and systemic IL-6 signaling 5,6.
Target Actions Organism AInterleukin-6 receptor subunit alpha antagonistantibodyHumans UHigh affinity immunoglobulin gamma Fc receptor I unknownHumans ULow affinity immunoglobulin gamma Fc region receptor II-a unknownHumans ULow affinity immunoglobulin gamma Fc region receptor II-b unknownHumans ULow affinity immunoglobulin gamma Fc region receptor III-A unknownHumans ULow affinity immunoglobulin gamma Fc region receptor III-B unknownHumans - Absorption
Sarilumab is shown to be well absorbed in RA patients after single SC administration with a maximum of serum concentration presented after 2 to 4 days. For the 150 mg every two weeks dose regimen, the AUC, Cmin and Cmax of sarilumab were 202 ± 120 mg.day/L, 6.35 ± 7.54 mg/L, and 20.0 ± 9.20 mg/L, respectively. For the 200 mg every two weeks dose regimen, the AUC, Cmin and Cmax of sarilumab were 395 ± 207 mg.day/L, 16.5 ± 14.1 mg/L, and 35.6 ± 15.2 mg/L, respectively 6.
- Volume of distribution
In patients with RA, the apparent volume of distribution at steady state was 7.3 L 6.
- Protein binding
Sarilumab is a covalent heterotetramer composed by two disulfide linked heavy chains covelently linked to a kappa light chain. The heavy chain has a IgG1 constant region with a single N-linked glycosylation site in the Fc portion of the molecule. 6 The complimentarity-determining regions (CDRs) within variable domains of both light and heavy chains combine to form the binding site for IL-6R. As Sarilumab is an IgG1 molecule, it presents Fc-effector function and it is prompt to bind to FcγRI, FcγRIIa, FCγRIIb, FcγRIIIa and FcγRIIIB. However, it does not induce Antibody-Dependant Cell-mediated Cytotoxicity (ADCC) or Complement-Dependant Cytotoxicity (CDC) 5.
- Metabolism
The metabolism of Sarilumab has not been characterized. As it is a monoclonal antibody, It is thought to be degraded into small peptides and amino acids [FDA file].
- Route of elimination
At high concentrations, Sarilumab is thought to be eliminated predominantly through a non-saturated proteolytic pathway, while at lower concentrations, the elimination will be done by saturable target-mediated elimination 1.
- Half-life
The half life will depend on the administered concentration. At 200 mg every 2 weeks, half-life is up to 10 days in patients with RA at steady state. At 150 mg every 2 weeks, half-life is up to 8 days in patients with RA at steady state. After the last steady state dose of 150 mg and 200 mg, the time to reach nondetectable concentration is 28 and 43 days, respectively 5.
- Clearance
Sarilumab is not eliminated via renal or hepatic pathways. RA patients have shown a trend toward higher clearance in presence of anti-sarilumab antibodies [FDA file].
- Adverse Effects
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Repeat dose exposure has been shown to produce a partially reversible decrease in neutophil count and a reversible decrease in fibrinogen 5.
- 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 Sarilumab. Abciximab The risk or severity of adverse effects can be increased when Abciximab is combined with Sarilumab. Abemaciclib The metabolism of Abemaciclib can be increased when combined with Sarilumab. Acalabrutinib The metabolism of Acalabrutinib can be increased when combined with Sarilumab. Acenocoumarol The serum concentration of Acenocoumarol can be increased when it is combined with Sarilumab. Adalimumab The risk or severity of infection can be increased when Adalimumab is combined with Sarilumab. Adenovirus type 7 vaccine live The risk or severity of infection can be increased when Adenovirus type 7 vaccine live is combined with Sarilumab. Aducanumab The risk or severity of adverse effects can be increased when Sarilumab is combined with Aducanumab. Albendazole The metabolism of Albendazole can be increased when combined with Sarilumab. Aldesleukin The risk or severity of adverse effects can be increased when Aldesleukin is combined with Sarilumab. 
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- 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 Kevzara Injection, solution 200 mg/1.14mL Subcutaneous sanofi-aventis U.S. LLC 2017-05-22 Not applicable US 
Kevzara Injection, solution 200 mg Subcutaneous Sanofi Aventis Groupe 2020-12-16 Not applicable EU 
Kevzara Injection, solution 200 mg Subcutaneous Sanofi Aventis Groupe 2020-12-16 Not applicable EU Kevzara Solution 200 mg / 1.14 mL Subcutaneous Sanofi Aventis 2017-02-08 Not applicable Canada 
Kevzara Injection, solution 200 mg Subcutaneous Sanofi Aventis Groupe 2020-12-16 Not applicable EU Kevzara Injection, solution 150 mg Subcutaneous Sanofi Aventis Groupe 2020-12-16 Not applicable EU Kevzara Injection, solution 200 mg Subcutaneous Sanofi Aventis Groupe 2020-12-16 Not applicable EU Kevzara Injection, solution 200 mg/1.14mL Subcutaneous sanofi-aventis U.S. LLC 2017-05-22 Not applicable US Kevzara Solution 200 mg / 1.14 mL Subcutaneous Sanofi Aventis 2018-06-21 Not applicable Canada Kevzara Injection, solution 150 mg Subcutaneous Sanofi Aventis Groupe 2020-12-16 Not applicable EU
Categories
- ATC Codes
- L04AC14 — Sarilumab
- Drug Categories
- Amino Acids, Peptides, and Proteins
- Antibodies
- Antibodies, Monoclonal
- Antineoplastic and Immunomodulating Agents
- Antirheumatic Agents
- Biologics for Rheumatoid Arthritis Treatment
- Blood Proteins
- Cytochrome P-450 CYP3A Inducers
- Cytochrome P-450 CYP3A Inhibitors
- Cytochrome P-450 CYP3A4 Inducers
- Cytochrome P-450 CYP3A4 Inducers (weak)
- Cytochrome P-450 CYP3A4 Inhibitors
- Cytochrome P-450 CYP3A4 Inhibitors (weak)
- Cytochrome P-450 Enzyme Inducers
- Cytochrome P-450 Enzyme Inhibitors
- Disease-modifying Antirheumatic Agents
- Globulins
- Immunoglobulins
- Immunoproteins
- Immunosuppressive Agents
- Immunotherapy
- Interleukin Inhibitors
- Interleukin-6 Receptor Antagonist
- Proteins
- 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
- NU90V55F8I
- CAS number
- 1189541-98-7
References
- General References
- Huizinga TW, Fleischmann RM, Jasson M, Radin AR, van Adelsberg J, Fiore S, Huang X, Yancopoulos GD, Stahl N, Genovese MC: Sarilumab, a fully human monoclonal antibody against IL-6Ralpha in patients with rheumatoid arthritis and an inadequate response to methotrexate: efficacy and safety results from the randomised SARIL-RA-MOBILITY Part A trial. Ann Rheum Dis. 2014 Sep;73(9):1626-34. doi: 10.1136/annrheumdis-2013-204405. Epub 2013 Dec 2. [Article]
- Genovese MC, Fleischmann R, Kivitz AJ, Rell-Bakalarska M, Martincova R, Fiore S, Rohane P, van Hoogstraten H, Garg A, Fan C, van Adelsberg J, Weinstein SP, Graham NM, Stahl N, Yancopoulos GD, Huizinga TW, van der Heijde D: Sarilumab Plus Methotrexate in Patients With Active Rheumatoid Arthritis and Inadequate Response to Methotrexate: Results of a Phase III Study. Arthritis Rheumatol. 2015 Jun;67(6):1424-37. doi: 10.1002/art.39093. [Article]
- Cooper S: Sarilumab for the treatment of rheumatoid arthritis. Immunotherapy. 2016;8(3):249-50. doi: 10.2217/imt.15.127. Epub 2016 Feb 9. [Article]
- Kaufman MB: Pharmaceutical Approval Update. P T. 2017 Sep;42(9):562-580. [Article]
- ema.europa [Link]
- Kevzara product monograph [Link]
- External Links
- FDA label
- Download (1.31 MB)
- MSDS
- Download (90.8 KB)
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 4 Completed Treatment Rheumatoid Arthritis 1 4 Not Yet Recruiting Treatment Atherosclerosis / Rheumatoid Arthritis 1 3 Active Not Recruiting Treatment Rheumatoid Arthritis 1 3 Completed Treatment Coronavirus Disease 2019 (COVID‑19) / Infections, Coronavirus 1 3 Completed Treatment Rheumatoid Arthritis 9 3 Recruiting Treatment Community-acquired Pneumonia, Influenza, COVID-19 / Coronavirus Disease 2019 (COVID‑19) 1 3 Recruiting Treatment Rheumatoid Arthritis 1 3 Terminated Treatment Giant Cell Arteritis (GCA) 1 3 Terminated Treatment Polymyalgia Rheumatica (PMR) 1 3 Terminated Treatment Rheumatoid Arthritis 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Injection, solution Parenteral; Subcutaneous 150 MG Injection, solution Parenteral; Subcutaneous 200 MG Injection, solution Subcutaneous 150 mg/1.14mL Injection, solution Subcutaneous 200 mg/1.14mL Solution Subcutaneous 150 mg / 1.14 mL Solution Subcutaneous 200 mg / 1.14 mL Injection, solution Subcutaneous 150 mg Injection, solution Subcutaneous 200 mg - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 69 °C (midpoint transition), 80 °C (whole IgG1) Dashivets, et al. PLOS ONE. 10. e0143520. 10.1371/journal.pone.0143520. (2015). 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
- AntagonistAntibody
- General Function
- Protein homodimerization activity
- Specific Function
- Part of the receptor for interleukin 6. Binds to IL6 with low affinity, but does not transduce a signal. Signal activation necessitate an association with IL6ST. Activation may lead to the regulati...
- Gene Name
- IL6R
- Uniprot ID
- P08887
- Uniprot Name
- Interleukin-6 receptor subunit alpha
- Molecular Weight
- 51547.015 Da
References
- Huizinga TW, Fleischmann RM, Jasson M, Radin AR, van Adelsberg J, Fiore S, Huang X, Yancopoulos GD, Stahl N, Genovese MC: Sarilumab, a fully human monoclonal antibody against IL-6Ralpha in patients with rheumatoid arthritis and an inadequate response to methotrexate: efficacy and safety results from the randomised SARIL-RA-MOBILITY Part A trial. Ann Rheum Dis. 2014 Sep;73(9):1626-34. doi: 10.1136/annrheumdis-2013-204405. Epub 2013 Dec 2. [Article]
- June RR, Olsen NJ: Room for more IL-6 blockade? Sarilumab for the treatment of rheumatoid arthritis. Expert Opin Biol Ther. 2016 Oct;16(10):1303-9. doi: 10.1080/14712598.2016.1217988. Epub 2016 Aug 8. [Article]
- Smolen JS, Landewe R, Bijlsma J, Burmester G, Chatzidionysiou K, Dougados M, Nam J, Ramiro S, Voshaar M, van Vollenhoven R, Aletaha D, Aringer M, Boers M, Buckley CD, Buttgereit F, Bykerk V, Cardiel M, Combe B, Cutolo M, van Eijk-Hustings Y, Emery P, Finckh A, Gabay C, Gomez-Reino J, Gossec L, Gottenberg JE, Hazes JMW, Huizinga T, Jani M, Karateev D, Kouloumas M, Kvien T, Li Z, Mariette X, McInnes I, Mysler E, Nash P, Pavelka K, Poor G, Richez C, van Riel P, Rubbert-Roth A, Saag K, da Silva J, Stamm T, Takeuchi T, Westhovens R, de Wit M, van der Heijde D: EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update. Ann Rheum Dis. 2017 Jun;76(6):960-977. doi: 10.1136/annrheumdis-2016-210715. Epub 2017 Mar 6. [Article]
- Kampan NC, Xiang SD, McNally OM, Stephens AN, Quinn MA, Plebanski M: Immunotherapeutic Interleukin-6 or Interleukin-6 receptor blockade in cancer: challenges and opportunities. Curr Med Chem. 2017 Jul 12. doi: 10.2174/0929867324666170712160621. [Article]
- Lin P: Targeting interleukin-6 for noninfectious uveitis. Clin Ophthalmol. 2015 Sep 11;9:1697-702. doi: 10.2147/OPTH.S68595. eCollection 2015. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Unknown
- General Function
- Receptor signaling protein activity
- Specific Function
- High affinity receptor for the Fc region of immunoglobulins gamma. Functions in both innate and adaptive immune responses.
- Gene Name
- FCGR1A
- Uniprot ID
- P12314
- Uniprot Name
- High affinity immunoglobulin gamma Fc receptor I
- Molecular Weight
- 42631.525 Da
References
- ema.europa [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Unknown
- General Function
- Not Available
- Specific Function
- Binds to the Fc region of immunoglobulins gamma. Low affinity receptor. By binding to IgG it initiates cellular responses against pathogens and soluble antigens. Promotes phagocytosis of opsonized ...
- Gene Name
- FCGR2A
- Uniprot ID
- P12318
- Uniprot Name
- Low affinity immunoglobulin gamma Fc region receptor II-a
- Molecular Weight
- 35000.42 Da
References
- ema.europa [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Unknown
- General Function
- Not Available
- Specific Function
- Receptor for the Fc region of complexed or aggregated immunoglobulins gamma. Low affinity receptor. Involved in a variety of effector and regulatory functions such as phagocytosis of immune complex...
- Gene Name
- FCGR2B
- Uniprot ID
- P31994
- Uniprot Name
- Low affinity immunoglobulin gamma Fc region receptor II-b
- Molecular Weight
- 34043.355 Da
References
- ema.europa [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Unknown
- General Function
- Not Available
- Specific Function
- Receptor for the Fc region of IgG. Binds complexed or aggregated IgG and also monomeric IgG. Mediates antibody-dependent cellular cytotoxicity (ADCC) and other antibody-dependent responses, such as...
- Gene Name
- FCGR3A
- Uniprot ID
- P08637
- Uniprot Name
- Low affinity immunoglobulin gamma Fc region receptor III-A
- Molecular Weight
- 29088.895 Da
References
- ema.europa [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Unknown
- General Function
- Not Available
- Specific Function
- Receptor for the Fc region of immunoglobulins gamma. Low affinity receptor. Binds complexed or aggregated IgG and also monomeric IgG. Contrary to III-A, is not capable to mediate antibody-dependent...
- Gene Name
- FCGR3B
- Uniprot ID
- O75015
- Uniprot Name
- Low affinity immunoglobulin gamma Fc region receptor III-B
- Molecular Weight
- 26215.64 Da
References
- ema.europa [Link]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- InhibitorInducer
- General Function
- Vitamin d3 25-hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
- Gene Name
- CYP3A4
- Uniprot ID
- P08684
- Uniprot Name
- Cytochrome P450 3A4
- Molecular Weight
- 57342.67 Da
References
- ema.europa [Link]
Drug created at October 20, 2016 20:46 / Updated at June 03, 2022 07:24