Array ( [0] => {{Short description|Biopharmaceutical for autoimmune diseases}} [1] => {{Infobox drug [2] => | image = Enbrel.jpg [3] => | width = 153 [4] => | alt = [5] => [6] => [7] => | pronounce = [8] => | tradename = Enbrel [9] => | Drugs.com = {{drugs.com|monograph|etanercept}} [10] => | MedlinePlus = a602013 [11] => | DailyMedID = Etanercept [12] => | pregnancy_AU = D [13] => | pregnancy_AU_comment = {{cite web | title=Etanercept Use During Pregnancy | website=Drugs.com | date=24 January 2020 | url=https://www.drugs.com/pregnancy/etanercept.html | access-date=13 August 2020}} [14] => | pregnancy_category = [15] => | routes_of_administration = [[Subcutaneous injection|Subcutaneous]] [16] => | class = [17] => | ATC_prefix = L04 [18] => | ATC_suffix = AB01 [19] => | ATC_supplemental = [20] => | biosimilars = etanercept-szzs, etanercept-ykro, Benepali, Brenzys,{{cite web | title=Health Canada New Drug Authorizations: 2016 Highlights | website=[[Health Canada]] | date=14 March 2017 | url=https://www.canada.ca/en/health-canada/services/publications/drugs-health-products/health-canada-new-drug-authorizations-2016-highlights.html | access-date=7 April 2024}} Erelzi,{{cite web | title=Arthritis | website=[[Health Canada]] | date=8 May 2018 | url=https://www.canada.ca/en/services/health/drug-health-products/drug-medical-device-highlights-2017/approved-drugs/arthritis.html | access-date=13 April 2024}}{{cite web | title=Regulatory Decision Summary for Erelzi | website=Drug and Health Products Portal | date=6 April 2017 | url=https://dhpp.hpfb-dgpsa.ca/review-documents/resource/RDS00226 | access-date=13 April 2024}} Etacept, Etera, Eticovo, Lifmior, Nepexto, Rymti [21] => [22] => [23] => | legal_AU = S4 [24] => | legal_AU_comment = [25] => | legal_BR = [26] => | legal_BR_comment = [27] => | legal_CA = Rx-only [28] => | legal_CA_comment = / Schedule D{{cite web | title=Rymti Summary Basis of Decision | website=[[Health Canada]] | date=23 October 2014 | url=https://hpr-rps.hres.ca/reg-content/summary-basis-decision-detailTwo.php?lang=en&linkID=SBD00623&lang=en | access-date=10 March 2023}} [29] => | legal_DE = [30] => | legal_DE_comment = [31] => | legal_NZ = [32] => | legal_NZ_comment = [33] => | legal_UK = POM [34] => | legal_UK_comment = {{cite web | title=Benepali 25 mg solution for injection in pre-filled syringe - Summary of Product Characteristics (SmPC) | website=(emc) | date=25 January 2021 | url=https://www.medicines.org.uk/emc/product/2708/smpc | access-date=12 June 2021}}{{cite web | title=Enbrel 25mg solution for injection in pre-filled pen - Summary of Product Characteristics (SmPC) | website=(emc) | date=8 June 2021 | url=https://www.medicines.org.uk/emc/product/11738/smpc | access-date=12 June 2021}}{{cite web | title=Erelzi 50 mg solution for injection in pre filled pen - Summary of Product Characteristics (SmPC) | website=(emc) | date=25 May 2021 | url=https://www.medicines.org.uk/emc/product/12517/smpc | access-date=12 June 2021}} [35] => | legal_US = Rx-only [36] => | legal_US_comment = {{cite web | title=Enbrel- etanercept solution Enbrel- etanercept kit | website=DailyMed | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a002b40c-097d-47a5-957f-7a7b1807af7f | access-date=17 April 2021}} [37] => | legal_EU = Rx-only [38] => | legal_EU_comment = {{cite web | title=Nepexto EPAR | website=European Medicines Agency | date=24 March 2020 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/nepexto | access-date=4 March 2023}}{{cite web | title=Nepexto Product information | website=Union Register of medicinal products | url=https://ec.europa.eu/health/documents/community-register/html/h1436.htm | access-date=3 March 2023}} [39] => | legal_UN = [40] => | legal_UN_comment = [41] => | legal_status = [42] => [43] => [44] => | bioavailability = 58–76% (SC) [45] => | protein_bound = [46] => | metabolism = [47] => | metabolites = [48] => | onset = [49] => | elimination_half-life = 70–132 hours [50] => | duration_of_action = [51] => | excretion = [52] => [53] => [54] => | CAS_number = 185243-69-0 [55] => | CAS_supplemental = [56] => | PubChem = [57] => | PubChemSubstance = 7847807 [58] => | IUPHAR_ligand = [59] => | DrugBank = DB00005 [60] => | ChemSpiderID = None [61] => | UNII = OP401G7OJC [62] => | KEGG = D00742 [63] => | ChEBI = [64] => | ChEMBL = 1201572 [65] => | NIAID_ChemDB = [66] => | PDB_ligand = [67] => | synonyms = [68] => [69] => [70] => | IUPAC_name = [71] => | C=2224 | H=3475 | N=621 | O=698 | S=36 [72] => | SMILES = [73] => | StdInChI = [74] => | StdInChI_comment = [75] => | StdInChIKey = [76] => | density = [77] => | density_notes = [78] => | melting_point = [79] => | melting_high = [80] => | melting_notes = [81] => | boiling_point = [82] => | boiling_notes = [83] => | solubility = [84] => | sol_units = [85] => | specific_rotation = [86] => }} [87] => [88] => '''Etanercept''', sold under the brand name '''Enbrel''' among others, is a [[biologic medical product]] that is used to treat [[autoimmune disease]]s by interfering with [[tumor necrosis factor]] (TNF), a soluble inflammatory cytokine, by acting as a [[TNF inhibitor]]. It has US [[Food and Drug Administration]] (FDA) approval to treat [[rheumatoid arthritis]], [[juvenile idiopathic arthritis]] and [[psoriatic arthritis]], [[Psoriasis|plaque psoriasis]] and [[ankylosing spondylitis]]. [[Tumor necrosis factor alpha]] (TNFα) is the "master regulator" of the inflammatory (immune) response in many organ systems. Autoimmune diseases are caused by an overactive immune response. Etanercept has the potential to treat these diseases by inhibiting TNF-alpha.{{cite journal | vauthors = Feldmann M, Maini RN | title = Lasker Clinical Medical Research Award. TNF defined as a therapeutic target for rheumatoid arthritis and other autoimmune diseases | journal = Nature Medicine | volume = 9 | issue = 10 | pages = 1245–1250 | date = October 2003 | pmid = 14520364 | doi = 10.1038/nm939 | s2cid = 52860838 }} [89] => [90] => Etanercept is a [[fusion protein]] produced by [[recombinant DNA]]. It fuses the TNF receptor to the constant end of the IgG1 antibody. First, the developers isolated the DNA sequence that codes the human gene for soluble [[CD120|TNF receptor 2]], which is a receptor that binds to tumor necrosis factor-alpha. Second, they isolated the DNA sequence that codes the human gene for the [[Fragment crystallizable region|Fc]] end of [[immunoglobulin G1]] (IgG1). Third, they linked the DNA for TNF receptor 2 to the DNA for IgG1 Fc. Finally, they expressed the linked DNA to produce a protein that links the protein for TNF receptor 2 to the protein for IgG1 Fc.{{Cite web|url=https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=103795|title = Drugs@FDA: FDA-Approved Drugs}} [91] => [92] => The prototypic fusion protein was first synthesized and shown to be highly active and unusually stable as a modality for blockade of TNF ''in vivo'' in the early 1990s by [[Bruce A. Beutler]], an academic researcher then at the [[University of Texas Southwestern Medical Center at Dallas]], and his colleagues.{{cite journal | vauthors = Peppel K, Crawford D, Beutler B | title = A tumor necrosis factor (TNF) receptor-IgG heavy chain chimeric protein as a bivalent antagonist of TNF activity | journal = The Journal of Experimental Medicine | volume = 174 | issue = 6 | pages = 1483–1489 | date = December 1991 | pmid = 1660525 | pmc = 2119031 | doi = 10.1084/jem.174.6.1483 }}{{cite journal | vauthors = Peppel K, Poltorak A, Melhado I, Jirik F, Beutler B | title = Expression of a TNF inhibitor in transgenic mice | journal = Journal of Immunology | volume = 151 | issue = 10 | pages = 5699–5703 | date = November 1993 | pmid = 7693816 | doi = 10.4049/jimmunol.151.10.5699 | s2cid = 10859938 }} [93] => [94] => These investigators also patented the protein,U.S. Patent number: 5,447,851 selling all rights to its use to [[Immunex]], a Seattle biotechnology company that was acquired by [[Amgen]] in 2002.{{cite web |url=http://www.dukemednews.org/news/article.php?id=9419 |title=Arthritis Drug Effective for Depression in Psoriasis Sufferers |access-date=2008-01-10 |archive-url=https://web.archive.org/web/20071020205003/http://www.dukemednews.org/news/article.php?id=9419 |archive-date=2007-10-20 |url-status=dead }} [95] => [96] => It is a large molecule, with a molecular weight of 150 [[kDa]], that binds to TNFα and decreases its role in disorders involving excess inflammation in humans and other animals, including [[autoimmune diseases]] such as [[ankylosing spondylitis]],{{cite journal | vauthors = Braun J, McHugh N, Singh A, Wajdula JS, Sato R | title = Improvement in patient-reported outcomes for patients with ankylosing spondylitis treated with etanercept 50 mg once-weekly and 25 mg twice-weekly | journal = Rheumatology | volume = 46 | issue = 6 | pages = 999–1004 | date = June 2007 | pmid = 17389658 | doi = 10.1093/rheumatology/kem069 | doi-access = free }} [[juvenile rheumatoid arthritis]], [[psoriasis]], [[psoriatic arthritis]], [[rheumatoid arthritis]], and, potentially, in a variety of other disorders mediated by excess TNFα. It is on the [[WHO Model List of Essential Medicines|World Health Organization's List of Essential Medicines]].{{cite book | vauthors = ((World Health Organization)) | title = World Health Organization model list of essential medicines: 21st list 2019 | year = 2019 | hdl = 10665/325771 | author-link = World Health Organization | publisher = World Health Organization | location = Geneva | id = WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO | hdl-access=free }} [97] => [98] => ==Medical uses== [99] => In the United States, etanercept is [[Indication (medicine)|indicated]] for: [100] => * Moderate to Severe [[Rheumatoid Arthritis]] (RA) (Nov 1998){{cite letter | vauthors = Siegel YP | recipient = Sally Gould | subject = Approval of Etanercept for treatment of rheumatoid arthritis | date = November 2, 1998 | access-date = April 14, 2015 | url = https://www.fda.gov/downloads/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/ApprovalApplications/TherapeuticBiologicApplications/ucm088659.pdf | publisher = U.S. [[Food and Drug Administration]] (FDA)}} [101] => * Moderate to Severe Polyarticular [[Juvenile Rheumatoid Arthritis]] (May 1999){{cite letter | vauthors = Weiss KD | recipient = Sally Gould | subject = Approval of Etanercept for treatment of polyarticular course juvenile rheumatoid arthritis (JRA) | date = May 27, 1999 | access-date = April 14, 2015 | url = https://www.fda.gov/downloads/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/ApprovalApplications/TherapeuticBiologicApplications/ucm088844.pdf | publisher = U.S. [[Food and Drug Administration]] (FDA)}} [102] => * [[Psoriatic Arthritis]] (Jan 2002){{cite letter | vauthors = Weiss KD | recipient = Sally Gould | subject = Approval of Etanercept for treatment of psoriatic arthritis | date = January 15, 2002 | access-date = April 14, 2015 | url = http://www.accessdata.fda.gov/drugsatfda_docs/appletter/2002/etanimm011502L.htm | publisher = U.S. [[Food and Drug Administration]] (FDA)}} [103] => * [[Ankylosing Spondylitis]] (AS) (July 2003){{cite letter | vauthors = Keegan P | recipient = Douglas Hunt | subject = Approval of Etanercept for treatment of ankylosing spondylitis | date = July 24, 2003 | access-date = April 14, 2015 | url = http://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/103795-5123_Enbrel_approv.pdf | publisher = U.S. [[Food and Drug Administration]] (FDA)}}{{cite journal | vauthors = Maxwell LJ, Zochling J, Boonen A, Singh JA, Veras MM, Tanjong Ghogomu E, Benkhalti Jandu M, Tugwell P, Wells GA | display-authors = 6 | title = TNF-alpha inhibitors for ankylosing spondylitis | journal = The Cochrane Database of Systematic Reviews | volume = 4 | issue = 4 | pages = CD005468 | date = April 2015 | pmid = 25887212 | doi = 10.1002/14651858.CD005468.pub2 }} [104] => * Moderate to Severe [[Plaque psoriasis|Plaque Psoriasis]] (April 2004){{cite letter | vauthors = Walton M | recipient = Douglas Hunt | subject = Approval of Etanercept for treatment of moderate to severe plaque psoriasis | date = April 30, 2004 | access-date = April 14, 2015 | url = http://www.accessdata.fda.gov/drugsatfda_docs/appletter/biologics/2004/103795_5149ltr.pdf | publisher = U.S. [[Food and Drug Administration]] (FDA)}} [105] => [106] => In the European Union, etanercept is indicated to treat: [107] => * moderate to severe active rheumatoid arthritis [108] => * severe, active and progressive rheumatoid arthritis [109] => * juvenile [[Takayasu's arteritis|idiopathic arthritis]] [110] => * [[polyarthritis]] (rheumatoid-factor-positive or -negative) and extended [[oligoarthritis]] in children and adolescents [111] => * active and progressive psoriatic arthritis [112] => * enthesitis-related arthritis [113] => * axial spondyloarthritis [114] => * severe active ankylosing spondylitis [115] => * severe non-radiographic axial spondyloarthritis [116] => * moderate to severe plaque psoriasis [117] => * chronic severe plaque psoriasis pediatric plaque psoriasis [118] => [119] => === Unrecognized uses === [120] => [121] => An American physician, Edward Tobinick, has attempted to use etanercept to treat chronic neurological dysfunction after [[stroke]] and [[brain injury]]{{cite news |publisher=Springer Select |date=October 31, 2012 |title=New hope for survivors of stroke and traumatic brain injury | url=https://www.springer.com/about+springer/media/springer+select?SGWID=0-11001-6-1394543-0 |access-date=November 17, 2018 }} and issued U.S.{{Cite patent|country=US|number=8900583|title=Methods for treatment of brain injury utilizing biologics|inventor = Tobinick EL |pubdate=2014-12-02}} and foreign patents. Writing for [[Science-Based Medicine]], [[Steven Novella]] said that it was "unethical for physicians to practice outside of their area of competence and expertise". Tobinick sued Novella in response, and lost.{{Cite web |date=2017-02-24 |title=Another Free Speech Win In Libel Lawsuit Disguised As A Trademark Complaint |url=https://abovethelaw.com/2017/02/another-free-speech-win-in-libel-lawsuit-disguised-as-a-trademark-complaint/ |access-date=2022-06-27 |website=Above the Law |language=en-US}} Of this treatment, the [[American Academy of Neurology]] advise "there is insufficient evidence to determine its effectiveness and that the treatment may be associated with adverse outcomes and high cost".{{cite web |publisher=American Academy of Neurology |title=Practice Advisory: Etanercept for Poststroke Disability |url=https://www.aan.com/Guidelines/home/GetGuidelineContent/747 |date=6 June 2016 |format=pdf}} [122] => [123] => == Adverse effects == [124] => [125] => On May 2, 2008, the US [[Food and Drug Administration]] (FDA) placed a [[black box warning]] on etanercept due to a number of serious infections associated with the drug.{{cite web|url=https://money.cnn.com/news/newsfeeds/articles/apwire/21965cf0a650a8b5897142bfcbccb427.htm |title=Wyeth and Amgen heighten warning of life-threatening infections on skin drug Enbrel |access-date=2008-05-02 |archive-url=https://web.archive.org/web/20080505133653/https://money.cnn.com/news/newsfeeds/articles/apwire/21965cf0a650a8b5897142bfcbccb427.htm |archive-date=2008-05-05 |url-status=dead }} Serious infections and [[sepsis]], including fatalities, have been reported with the use of etanercept including reactivation of [[latent tuberculosis]] and [[hepatitis B]] infections.{{cite conference | url=https://www.fda.gov/ohrms/dockets/ac/01/briefing/3779b2_01_cber_safety%20_revision2.pdf | title=Safety Update on TNF- α Antagonists: Infliximab and Etanercept | publisher=U.S. [[Food and Drug Administration]] (FDA) | access-date=20 December 2013 | pages=13–14 | conference= | archive-date=24 September 2015 | archive-url=https://web.archive.org/web/20150924170456/http://www.fda.gov/ohrms/dockets/ac/01/briefing/3779b2_01_cber_safety%20_revision2.pdf | url-status=dead }} [126] => [127] => [[Injection site reaction]]s such as redness and pain are common, occurring in approximately 11.4% of cases.{{cite journal | vauthors = Kim PJ, Lansang RP, Vender R | title = A Systematic Review and Meta-Analysis of Injection Site Reactions in Randomized-Controlled Trials of Biologic Injections | journal = Journal of Cutaneous Medicine and Surgery | volume = 27 | issue = 4 | pages = 358–367 | date = July 2023 | pmid = 37533141 | doi = 10.1177/12034754231188444 | pmc = 10486173 }} [128] => [129] => == Mechanism of action == [130] => Etanercept reduces the effect of naturally present TNF, and hence is a [[TNF inhibitor]], functioning as a [[decoy receptor]] that binds to TNF.{{cite journal | vauthors = Zalevsky J, Secher T, Ezhevsky SA, Janot L, Steed PM, O'Brien C, Eivazi A, Kung J, Nguyen DH, Doberstein SK, Erard F, Ryffel B, Szymkowski DE | display-authors = 6 | title = Dominant-negative inhibitors of soluble TNF attenuate experimental arthritis without suppressing innate immunity to infection | journal = Journal of Immunology | volume = 179 | issue = 3 | pages = 1872–1883 | date = August 2007 | pmid = 17641054 | doi = 10.4049/jimmunol.179.3.1872 | doi-access = free }} [131] => [132] => Tumor necrosis factor-alpha (TNFα) is a [[cytokine]] produced by [[lymphocyte]]s and [[macrophage]]s, two types of [[white blood cell]]s. It mediates the immune response by attracting additional white blood cells to sites of [[inflammation]] and through additional molecular mechanisms that initiate and amplify inflammation. Inhibition of its action by etanercept reduces the inflammatory response, which is especially useful for treating [[autoimmune disease]]s. [133] => [134] => There are two types of TNF [[receptor (biochemistry)|receptor]]s: those found embedded in white blood cells that respond to TNF by releasing other [[cytokine]]s, and ''soluble'' TNF receptors that are used to deactivate TNF and blunt the immune response. In addition, TNF receptors are found on the surface of virtually all nucleated cells (red blood cells, which are not nucleated, do not contain TNF receptors on their surface). Etanercept mimics the inhibitory effects of naturally occurring soluble TNF receptors, the difference being that etanercept, because it is a fusion protein rather than a simple TNF receptor, has a greatly extended half-life in the bloodstream, and therefore a more profound and long-lasting biologic effect than a naturally occurring soluble TNF receptor.{{cite journal | vauthors = Madhusudan S, Muthuramalingam SR, Braybrooke JP, Wilner S, Kaur K, Han C, Hoare S, Balkwill F, Ganesan TS | display-authors = 6 | title = Study of etanercept, a tumor necrosis factor-alpha inhibitor, in recurrent ovarian cancer | journal = Journal of Clinical Oncology | volume = 23 | issue = 25 | pages = 5950–5959 | date = September 2005 | pmid = 16135466 | doi = 10.1200/JCO.2005.04.127 }} [135] => [136] => == Structure == [137] => Etanercept is made from the combination of two naturally occurring soluble human 75-kilodalton TNF receptors linked to an Fc portion of an IgG1.{{cite journal | vauthors = Smola MG, Soyer HP, Scharnagl E | title = Surgical treatment of dermatofibrosarcoma protuberans. A retrospective study of 20 cases with review of literature | journal = European Journal of Surgical Oncology | volume = 17 | issue = 5 | pages = 447–453 | date = October 1991 | pmid = 1936291 }} The effect is an artificially engineered dimeric fusion protein. Etanercept is a complex molecule containing 6 N-glycans, up to 14 O-glycans and 29 disulfide bridge structures.{{cite journal | vauthors = Houel S, Hilliard M, Yu YQ, McLoughlin N, Martin SM, Rudd PM, Williams JP, Chen W | display-authors = 6 | title = N- and O-glycosylation analysis of etanercept using liquid chromatography and quadrupole time-of-flight mass spectrometry equipped with electron-transfer dissociation functionality | journal = Analytical Chemistry | volume = 86 | issue = 1 | pages = 576–584 | date = January 2014 | pmid = 24308717 | doi = 10.1021/ac402726h }}{{cite journal | vauthors = Mukai Y, Nakamura T, Yoshikawa M, Yoshioka Y, Tsunoda S, Nakagawa S, Yamagata Y, Tsutsumi Y | display-authors = 6 | title = Solution of the structure of the TNF-TNFR2 complex | journal = Science Signaling | volume = 3 | issue = 148 | pages = ra83 | date = November 2010 | pmid = 21081755 | doi = 10.1126/scisignal.2000954 | s2cid = 24226117 }}{{cite journal | vauthors = Lamanna WC, Mayer RE, Rupprechter A, Fuchs M, Higel F, Fritsch C, Vogelsang C, Seidl A, Toll H, Schiestl M, Holzmann J | display-authors = 6 | title = The structure-function relationship of disulfide bonds in etanercept | journal = Scientific Reports | volume = 7 | issue = 1 | pages = 3951 | date = June 2017 | pmid = 28638112 | pmc = 5479810 | doi = 10.1038/s41598-017-04320-5 | bibcode = 2017NatSR...7.3951L }} [138] => [139] => ==History== [140] => The first etanercept-related patent was filed by [[Immunex]] on September 5, 1989.{{cite journal | vauthors = Norman P | title = Enbrel and etanercept biosimilars: a tale of two patent systems | journal = Pharmaceutical Patent Analyst | volume = 6 | issue = 1 | pages = 5–7 | date = January 2017 | pmid = 28201948 | doi = 10.4155/ppa-2016-0043 }} The fusion protein was developed by Bruce A. Beutler, an academic researcher then at the University of Texas Southwestern Medical Center at Dallas, and colleagues, who patented it and licensed the rights in 1995 to Immunex.{{cite web | title=A three-decade monopoly: How Amgen built a patent thicket around its top-selling drug | date=November 1, 2021 | vauthors = Gardner J | url=https://www.biopharmadive.com/news/amgen-enbrel-patent-thicket-monopoly-biosimilar/609042/}} Another patent on such fusion protein technology from Brian Seed at [[Massachusetts General Hospital]] was licensed to Immmunex in 1997.{{cite web| vauthors = Kowalczyk L | date=March 24, 2002 |title= Lucrative Licensing Deals With Drug, Biotech Firms Are Raising Ethics Issues For Hospitals| url=https://www.sskrplaw.com/lucrative-licensing-deals-with-drug-biotech-firms-are-raising-et.html}} [141] => [142] => Etanercept was approved for use in the United States in November 1998.{{cite web | title=Etanercept Product Approval Information - Licensing Action 12/2/98 | website=U.S. [[Food and Drug Administration]] (FDA) | date=1 April 2016 | url=https://www.fda.gov/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/ApprovalApplications/TherapeuticBiologicApplications/ucm080536.htm | archive-url=https://web.archive.org/web/20170118085127/https://www.fda.gov/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/ApprovalApplications/TherapeuticBiologicApplications/ucm080536.htm | archive-date=18 January 2017 | url-status=dead | access-date=4 June 2020}} [143] => [144] => Etanercept was approved for use in the European Union in February 2000.{{cite web | title=Enbrel EPAR | website=[[European Medicines Agency]] (EMA) | date=17 September 2018 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/enbrel | access-date=2 April 2020}} Text was copied from this source which is © European Medicines Agency. Reproduction is authorized provided the source is acknowledged. [145] => [146] => ==Society and culture== [147] => [148] => ===Economics=== [149] => The US retail price of etanercept has risen over time. In 2008, the cost of etanercept was $1,500 per month or $18,000 per year.[http://seattletimes.com/html/health/2008120449_drugs18m.html "What's behind the whopping price tags on the newest generation of drugs:] The story behind the production of Enbrel, Amgen's popular rheumatoid arthritis drug, provides insights as to why bioengineered drugs are so expensive." Carol M. Ostrom, Seattle Times, August 18, 2008 By 2011, the cost had exceeded $20,000 per year.{{cite news | title=Amgen's New Enbrel Patent May Undercut Health Care Plan | website=The New York Times | date=23 November 2011 | url=https://www.nytimes.com/2011/11/23/business/amgens-new-enbrel-patent-may-undercut-health-care-plan.html | access-date=10 March 2023 | vauthors = Pollock A }}[http://bostonherald.com/news/columnists/view/2011_1103painful_reality "Co-pay hike a painful reality; Miracle drug monthly cost jumps from $42 to $600"] {{Webarchive|url=https://archive.today/20130118110008/http://bostonherald.com/news/columnists/view/2011_1103painful_reality |date=2013-01-18 }}, Margery Eagan, Boston Herald, November 3, 2011 In 2013, a survey by the International Federation of Health Plans (IFHP) found that the average US cost for etanercept was $2,225 per month, or $26,700 per year.{{cite web |url=https://static1.squarespace.com/static/518a3cfee4b0a77d03a62c98/t/534fc9ebe4b05a88e5fbab70/1397737963288/2013+iFHP+FINAL+4+14+14.pdf |title=2013 Comparative Price Report |publisher=International Federation of Health Plans |access-date=24 November 2017 |archive-date=22 October 2017 |archive-url=https://web.archive.org/web/20171022020959/http://static1.squarespace.com/static/518a3cfee4b0a77d03a62c98/t/534fc9ebe4b05a88e5fbab70/1397737963288/2013+iFHP+FINAL+4+14+14.pdf |url-status=dead }} The IFHP report also found wide variation in prices charged to various US health plans, between $1,946 per month at the 25th percentile and $4,006 per month at the 95th percentile. [150] => [151] => Etanercept is more expensive in the US than in other countries. As of 2013, average monthly costs in surveyed nations ranged from $1,017 in Switzerland to $1,646 in Canada, compared to an average monthly cost of $2,225 per month in the US. [152] => [153] => Amgen sells etanercept within the US and Canada, while [[Pfizer]], Inc. sells the drug outside of the US and Canada. Sales within the US and Canada were $3.5 billion in 2010. Sales of etanercept outside the US and Canada were $3.3 billion in 2010.{{cite web|url=https://www.sec.gov/Archives/edgar/data/78003/000119312511048877/dex13.htm |title=Portions of the 2010 Financial Report |publisher=Sec.gov |access-date=2019-06-05}} [154] => [155] => ===Patents=== [156] => The patent on etanercept was set to expire on October 23, 2012,{{cite web | url=http://www.uspto.gov/patents/resources/terms/156.html | title=Patent Terms Extended Under 35 USC §156 | access-date=2009-12-09 | archive-date=2010-02-24 | archive-url=https://web.archive.org/web/20100224023842/http://www.uspto.gov/patents/resources/terms/156.html | url-status=dead }} but, in the United States, a second patent, granting exclusivity for another 16 years, has been granted.{{cite web | url=http://www.gabionline.net/Biosimilars/News/New-Amgen-Enbrel-patent-could-block-biosimilars-until-2028 | title=New Amgen Enbrel patent could block biosimilars until 2028 | date=2011-11-25 | access-date=2019-07-14}} [157] => [158] => Before the extension it seemed unlikely that a generic would have been available. As a biologic, etanercept is subject to different laws from those applicable to chemical formulations. Many countries do not permit the manufacture of generic biologics. However, the European Union and the United States ([https://www.fda.gov/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/ApprovalApplications/TherapeuticBiologicApplications/Biosimilars/ Biologics Price Competition and Innovation Act of 2009]) do have in place a system to approve generic biologics ([[biosimilars]]) which "requires mandatory clinical testing and periodic review".{{cite web|url=https://scholarship.law.duke.edu/cgi/viewcontent.cgi?referer=https://en.wikipedia.org/&httpsredir=1&article=1184&context=dltr |title=The Future of Generic Biologics: Should the United States "Follow-On" the European Pathway? | vauthors = Kaldre I |date=2008 |website=www.law.duke.edu |access-date=2019-06-05}} [159] => [160] => In April 2013, the Indian pharma major [[Cipla]] made an announcement about launching the first biosimilar of Etanercept in India under the brand name Etacept for the treatment of rheumatic disorders.{{cite web |url=http://www.cipla.com/CiplaSite/Media/PDF/News-Archives/Press-Release-Launch-of-first-biosimilar-of-Etanercept-in-India.pdf?ext=.pdf |title=Cipla - Home |publisher=Cipla.com |access-date=2019-06-05 |archive-date=2013-05-01 |archive-url=https://web.archive.org/web/20130501202841/http://www.cipla.com/CiplaSite/Media/PDF/News-Archives/Press-Release-Launch-of-first-biosimilar-of-Etanercept-in-India.pdf?ext=.pdf |url-status=dead }} [161] => [162] => ===Biosimilars=== [163] => {{see also|Biosimilars}} [164] => [165] => In January 2016, Benepali was approved for use in the European Union.{{cite web | title=Benepali EPAR | website=[[European Medicines Agency]] (EMA) | date=17 September 2018 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/benepali | access-date=2 April 2020}} [166] => [167] => In February 2017, Lifmior was approved for use in the European Union.{{cite web | title=Lifmior EPAR | website=[[European Medicines Agency]] (EMA) | date=17 September 2018 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/lifmior | access-date=2 April 2020}} It was withdrawn from the market in February 2020.{{cite web | title=Public statement on Lifmior: Withdrawal of the marketing authorisation in the European Union | url=https://www.ema.europa.eu/documents/public-statement/public-statement-lifmior-withdrawal-marketing-authorisation-european-union_en.pdf | access-date=2 April 2020}} [168] => [169] => In June 2017, Erelzi was approved for use in the European Union.{{cite web | title=Erelzi EPAR | website=[[European Medicines Agency]] (EMA) | date=17 September 2018 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/erelzi | access-date=2 April 2020}} [170] => [171] => In March 2019, YLB113 (Etanercept biosimilar by YL Biologics) was approved in Japan.{{Cite web|title=Japanese approval for Lupin's etanercept biosimilar|url=https://www.gabionline.net/biosimilars/news/Japanese-approval-for-Lupin-s-etanercept-biosimilar}} [172] => [173] => In May 2020, Nepexto was approved for use in the European Union. [174] => [175] => Rymti and Etera were approved for medical use in Australia in October 2020.{{cite web | title=Australian Public Assessment Report for Etanercept | date= Feb 2021 | url=https://www.tga.gov.au/sites/default/files/auspar-etanercept-210224.pdf }}{{cite web | title=AusPAR: Etanercept | website=[[Therapeutic Goods Administration]] (TGA) | date=25 February 2021 | url=https://www.tga.gov.au/auspar/auspar-etanercept-3 | access-date=12 June 2021}}{{cite web | title=Rymti ARTG | website=[[Therapeutic Goods Administration]] (TGA) | url=https://tga-search.clients.funnelback.com/s/search.html?collection=tga-artg&profile=record&meta_i=309830 | access-date=12 June 2021 | archive-date=13 June 2021 | archive-url=https://web.archive.org/web/20210613063803/https://tga-search.clients.funnelback.com/s/search.html?collection=tga-artg&profile=record&meta_i=309830 | url-status=dead }}{{cite web | title=Etera ARTG | website=[[Therapeutic Goods Administration]] (TGA) | url=https://tga-search.clients.funnelback.com/s/search.html?collection=tga-artg&profile=record&meta_i=309829 | access-date=12 June 2021 | archive-date=13 June 2021 | archive-url=https://web.archive.org/web/20210613063806/https://tga-search.clients.funnelback.com/s/search.html?collection=tga-artg&profile=record&meta_i=309829 | url-status=dead }} [176] => [177] => == References == [178] => {{reflist}} [179] => [180] => {{Immunosuppressants}} [181] => {{Cytokine receptor modulators}} [182] => {{Portal bar | Medicine}} [183] => [184] => [[Category:TNF inhibitors]] [185] => [[Category:Amgen]] [186] => [[Category:Recombinant proteins]] [187] => [[Category:Immunosuppressants]] [188] => [[Category:Drugs developed by Wyeth]] [189] => [[Category:Drugs developed by Pfizer]] [190] => [[Category:Drugs developed by Novartis]] [191] => [[Category:World Health Organization essential medicines]] [192] => [[Category:Disease-modifying antirheumatic drugs]] [] => )
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Etanercept

Etanercept is a biologic response modifier medication commonly used to treat autoimmune diseases such as rheumatoid arthritis, psoriasis, and ankylosing spondylitis. It is administered via injection and works by inhibiting the action of tumor necrosis factor (TNF), a protein involved in inflammation.

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It is administered via injection and works by inhibiting the action of tumor necrosis factor (TNF), a protein involved in inflammation. Etanercept is a fusion protein made up of two components: a soluble TNF receptor and a human immunoglobulin G1 Fc region. By binding to TNF and preventing it from signaling immune cells, etanercept helps reduce inflammation and alleviate symptoms associated with autoimmune diseases. This Wikipedia page provides detailed information about the pharmacology, clinical uses, adverse effects, and contraindications of etanercept, as well as its history, development, and regulatory approval. It also discusses the various biosimilar versions of etanercept that have been developed and provides references for further reading.

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