Wikipedia:WikiProject Chemicals/Chembox validation/VerifiedDataSandbox and Tralokinumab: Difference between pages

{{Short description|Monoclonal antibody}}

{{Use dmy dates|date=July 2022}}

{{Infobox drug

| Watchedfields = changed

| verifiedrevid = 470612083

| image = Tralokinumab 5L6Y.png

| caption = Tralokinumab [[fragment antigen-binding|Fab fragment]] bound to IL-13. From [[Protein Data Bank|PDB]] {{PDB2|5L6Y}}.

<!-- Monoclonal antibody data -->

| target = [[interleukin 13|IL-13]]

<!-- Clinical data -->

| pronounce = {{IPAc-en|ˌ|t|r|eɪ|l|ə|ˈ|k|ɪ|nj|ʊ|m|æ|b}}<br />{{respell|TRAY|lə|KIN|yuu|mab}}

| tradename = Adtralza, Adbry

| DailyMedID = Tralokinumab

| pregnancy_AU_comment =

| pregnancy_category=

| routes_of_administration = [[Subcutaneous injection|Subcutaneous]]

| class =

| ATC_prefix = D11

| ATC_suffix = AH07

| ATC_supplemental =

<!-- Legal status -->

| legal_AU = <!-- S2, S3, S4, S5, S6, S7, S8, S9 or Unscheduled -->

| legal_AU_comment =

| legal_BR = <!-- OTC, A1, A2, A3, B1, B2, C1, C2, C3, C4, C5, D1, D2, E, F -->

| legal_BR_comment =

| legal_CA = Rx-only

| legal_CA_comment = /{{nbsp}}Schedule D<ref>{{cite web | title=Summary Basis of Decision (SBD) for Adtralza | website=Health Canada | date=23 October 2014 | url=https://hpr-rps.hres.ca/reg-content/summary-basis-decision-detailTwo.php?linkID=SBD00586&lang=en | access-date=29 May 2022 | archive-date=29 May 2022 | archive-url=https://web.archive.org/web/20220529191702/https://hpr-rps.hres.ca/reg-content/summary-basis-decision-detailTwo.php?linkID=SBD00586&lang=en | url-status=live }}</ref><ref>{{cite web | title=Health product highlights 2021: Annexes of products approved in 2021 | website=[[Health Canada]] | date=3 August 2022 | url=https://www.canada.ca/en/health-canada/services/publications/drugs-health-products/health-product-highlights-2021/appendices.html | access-date=25 March 2024}}</ref>

| legal_DE = <!-- Anlage I, II, III or Unscheduled -->

| legal_DE_comment =

| legal_NZ = <!-- Class A, B, C -->

| legal_NZ_comment =

| legal_UK = POM

| legal_UK_comment = <ref name="Adtralza SmPC">{{cite web | title=Adtralza 150 mg solution for injection in pre-filled syringe - Summary of Product Characteristics (SmPC) | website=(emc) | date=5 July 2021 | url=https://www.medicines.org.uk/emc/product/12725/smpc | access-date=9 July 2021 | archive-date=9 July 2021 | archive-url=https://web.archive.org/web/20210709203202/https://www.medicines.org.uk/emc/product/12725/smpc | url-status=live }}</ref>

| legal_US = Rx-only

| legal_US_comment = <ref name="Adbry FDA label">{{cite web | title=Adbry- tralokinumab-ldrm injection, solution | website=DailyMed | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d8020b69-3001-44e2-9b5d-5f93d9aaf6e1 | access-date=13 January 2022 | archive-date=13 January 2022 | archive-url=https://web.archive.org/web/20220113065139/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d8020b69-3001-44e2-9b5d-5f93d9aaf6e1 | url-status=live }}</ref>

| legal_EU = Rx-only

| legal_EU_comment = <ref name="Adtralza EPAR">{{cite web | title=Adtralza EPAR | website=[[European Medicines Agency]] (EMA) | date=20 April 2021 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/adtralza | access-date=9 July 2021 | archive-date=29 June 2021 | archive-url=https://web.archive.org/web/20210629030501/https://www.ema.europa.eu/en/medicines/human/EPAR/adtralza | url-status=live }} Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.</ref><ref>{{cite web | title=Adtralza Product information | website=Union Register of medicinal products | url=https://ec.europa.eu/health/documents/community-register/html/h1554.htm | access-date=3 March 2023}}</ref>

| legal_UN = <!-- N I, II, III, IV / P I, II, III, IV -->

| legal_UN_comment =

| legal_status = Rx-only<ref name="LEO Pharma PR" />

<!-- Pharmacokinetic data -->

| metabolites =

| onset =

| duration_of_action =

<!-- Identifiers -->

| CAS_number_Ref = {{cascite|changed|??}}

| CAS_number = 1044515-88-9

| CAS_supplemental =

| IUPHAR_ligand =

| DrugBank_Ref = {{drugbankcite|correct|drugbank}}

| DrugBank = DB12169

| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}}

| ChemSpiderID = none

| UNII_Ref = {{fdacite|changed|FDA}}

| UNII = GK1LYB375A

| KEGG_Ref =

| KEGG = D09979

| ChEBI_Ref =

| ChEBI =

| ChEMBL_Ref =

| ChEMBL =

| NIAID_ChemDB =

| PDB_ligand =

| synonyms = CAT-354, tralokinumab-ldrm

<!-- Chemical and physical data -->

| C=6374 | H=9822 | N=1698 | O=2014 | S=44

| SMILES =

| StdInChI =

| StdInChI_comment =

| StdInChIKey =

| density =

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| specific_rotation =

'''Tralokinumab''' sold under the brand names '''Adtralza''' (EU/UK) and '''Adbry''' (US) among others, is a [[human monoclonal antibody]] used for the treatment of [[atopic dermatitis]].<ref name="Adtralza SmPC" /><ref name="Adtralza EPAR" /> Tralokinumab targets the cytokine [[interleukin 13]].<ref>{{cite journal | vauthors = Kopf M, Bachmann MF, Marsland BJ | title = Averting inflammation by targeting the cytokine environment | journal = Nature Reviews. Drug Discovery | volume = 9 | issue = 9 | pages = 703–18 | date = September 2010 | pmid = 20811382 | doi = 10.1038/nrd2805 | s2cid = 23769909 }}</ref>

The most common side effects include upper respiratory tract infections (colds and other infections of the nose and throat), reactions at the injection site, and redness and discomfort in the eye.<ref name="Adtralza EPAR" />

Tralokinumab was approved for medical use in the European Union and in the United Kingdom in June 2021.<ref name="Adtralza SmPC" /><ref name="Adtralza EPAR" /><ref>{{cite press release | title=LEO Pharma announces European Commission approval of Adtralza (tralokinumab) as the first and only treatment specifically targeting IL-13 for adults with moderate-to-severe atopic dermatitis | publisher=LEO Pharma | via=Business Wire | date=22 June 2021 | url=https://www.businesswire.com/news/home/20210621005564/en/LEO-Pharma-announces-European-Commission-approval-of-Adtralza%C2%AE-tralokinumab-as-the-first-and-only-treatment-specifically-targeting-IL-13-for-adults-with-moderate-to-severe-atopic-dermatitis | access-date=22 January 2023 | archive-date=26 October 2021 | archive-url=https://web.archive.org/web/20211026215703/https://www.businesswire.com/news/home/20210621005564/en/LEO-Pharma-announces-European-Commission-approval-of-Adtralza%C2%AE-tralokinumab-as-the-first-and-only-treatment-specifically-targeting-IL-13-for-adults-with-moderate-to-severe-atopic-dermatitis | url-status=live }}</ref> It was approved for medical use in the United States in December 2021.<ref name="LEO Pharma PR" /><ref>{{cite web | title=Drug Approval Package: Adbry | website=U.S. [[Food and Drug Administration]] (FDA) | date=25 January 2022 | url=https://www.accessdata.fda.gov/drugsatfda_docs/nda/2022/761180Orig1s000TOC.cfm | access-date=22 January 2023 | archive-date=11 October 2022 | archive-url=https://web.archive.org/web/20221011012023/https://www.accessdata.fda.gov/drugsatfda_docs/nda/2022/761180Orig1s000TOC.cfm | url-status=live }}</ref><ref name="Adbry FDA label" /> The U.S. [[Food and Drug Administration]] (FDA) considers it to be a [[first-in-class medication]].<ref name="New Drug Therapy Approvals 2021">{{cite report | title=Advancing Health Through Innovation: New Drug Therapy Approvals 2021 | website=U.S. [[Food and Drug Administration]] (FDA) | date=13 May 2022 | url=https://www.fda.gov/media/155227/download | format=PDF | access-date=22 January 2023 | archive-date=6 December 2022 | archive-url=https://web.archive.org/web/20221206210020/https://www.fda.gov/media/155227/download | url-status=live }} {{PD-notice}}</ref>

== Medical uses ==

Tralokinumab is [[Indication (medicine)|indicated]] for the treatment of moderate-to-severe atopic dermatitis in adults who are candidates for systemic therapy.<ref name="Adtralza EPAR" /><ref name="Adtralza SmPC" />

In the United States, tralokinumab is indicated for the treatment of moderate-to-severe atopic dermatitis in adults whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable.<ref name="Adbry FDA label" /><ref name="LEO Pharma PR">{{cite press release | title=LEO Pharma announces FDA approval of Adbry (tralokinumab-ldrm) as the first and only treatment specifically targeting IL-13 for adults with moderate-to-severe atopic dermatitis | publisher=LEO Pharma | via=Business Wire | date=28 December 2021 | url=https://www.businesswire.com/news/home/20211227005159/en/LEO-Pharma-announces-FDA-approval-of-Adbry%E2%84%A2-tralokinumab-ldrm-as-the-first-and-only-treatment-specifically-targeting-IL-13-for-adults-with-moderate-to-severe-atopic-dermatitis | access-date=22 January 2023 | archive-date=5 October 2022 | archive-url=https://web.archive.org/web/20221005063337/https://www.businesswire.com/news/home/20211227005159/en/LEO-Pharma-announces-FDA-approval-of-Adbry%25E2%2584%25A2-tralokinumab-ldrm-as-the-first-and-only-treatment-specifically-targeting-IL-13-for-adults-with-moderate-to-severe-atopic-dermatitis | url-status=live }}</ref>

== Discovery and development ==

Tralokinumab was discovered by [[Cambridge Antibody Technology]] scientists<ref name="peds.oxfordjournals.org">{{cite journal | vauthors = Thom G, Cockroft AC, Buchanan AG, Candotti CJ, Cohen ES, Lowne D, Monk P, Shorrock-Hart CP, Jermutus L, Minter RR | display-authors = 6 | title = Probing a protein-protein interaction by in vitro evolution | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 103 | issue = 20 | pages = 7619–24 | date = May 2006 | pmid = 16684878 | pmc = 1458619 | doi = 10.1073/pnas.0602341103 | trans-title = P | bibcode = 2006PNAS..103.7619T | doi-access = free }}</ref><ref>{{cite journal | vauthors = May RD, Monk PD, Cohen ES, Manuel D, Dempsey F, Davis NH, Dodd AJ, Corkill DJ, Woods J, Joberty-Candotti C, Conroy LA, Koentgen F, Martin EC, Wilson R, Brennan N, Powell J, Anderson IK | display-authors = 6 | title = Preclinical development of CAT-354, an IL-13 neutralizing antibody, for the treatment of severe uncontrolled asthma | journal = British Journal of Pharmacology | volume = 166 | issue = 1 | pages = 177–93 | date = May 2012 | pmid = 21895629 | pmc = 3415647 | doi = 10.1111/j.1476-5381.2011.01659.x }}</ref><ref name=":0">{{Citation|title = Human Antibody Molecules for Il-13|url = https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2005007699&recNum=238&docAn=GB2004003059&queryString=(FP/antibody)%2520&maxRec=11743|access-date = 26 July 2015|archive-date = 8 February 2016|archive-url = https://web.archive.org/web/20160208015329/https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2005007699&recNum=238&docAn=GB2004003059&queryString=%28FP%2Fantibody%29%252520&maxRec=11743|url-status = live}}</ref> using protein optimization based on [[Ribosome display|Ribosome Display]].<ref>{{cite journal | vauthors = Jermutus L, Honegger A, Schwesinger F, Hanes J, Plückthun A | title = Tailoring in vitro evolution for protein affinity or stability | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 98 | issue = 1 | pages = 75–80 | date = January 2001 | pmid = 11134506 | pmc = 14547 | doi = 10.1073/pnas.98.1.75 | bibcode = 2001PNAS...98...75J | doi-access = free }}</ref> They used the extensive data sets from ribosome display to patent protect CAT-354 in a world-first of sequence-activity-relationship claims.<ref name=":0" /> In 2004, clinical development of CAT-354 was initiated with this first study completing in 2005.<ref name=":1">{{cite web | title = Tralokinumab | url = http://adisinsight.springer.com/drugs/800019573 | work = Adis Insight | publisher = Springer Nature Switzerland AG | access-date = 20 February 2016 | archive-date = 3 March 2016 | archive-url = https://web.archive.org/web/20160303140747/http://adisinsight.springer.com/drugs/800019573 | url-status = live }}</ref> On 21 July 2011, [[MedImmune]] LLC initiated a Phase IIb, randomized, double-blind study to evaluate the efficacy of tralokinumab in adults with asthma.<ref>{{ClinicalTrialsGov|NCT01402986|A Phase 2b, Randomized, Double-blind Study to Evaluate the Efficacy of Tralokinumab in Adults With Asthma}}</ref><ref>{{cite web|title=Pipeline|url=http://www.medimmune.com/research/pipeline|work=MedImmune|access-date=11 June 2013|archive-date=7 August 2013|archive-url=https://web.archive.org/web/20130807040800/http://www.medimmune.com/research/pipeline|url-status=live}}</ref><ref>{{cite web|title=Studies found for CAT-354|url=http://www.clinicaltrials.gov/ct2/results?term=CAT-354|work=ClinicalTrials.gov|access-date=11 June 2013|archive-date=30 July 2013|archive-url=https://web.archive.org/web/20130730054724/http://www.clinicaltrials.gov/ct2/results?term=CAT-354|url-status=live}}</ref>

In 2016, MedImmune and AstraZeneca started developing tralokinumab for asthma (Phase III) and atopic dermatitis (Phase IIb) while clinical development for moderate-to-severe [[ulcerative colitis]] and idiopathic pulmonary fibrosis (IPF) have been discontinued.<ref name=":1" /> In July of that year AstraZeneca licensed tralokinumab to [[Leo Pharma]] for skin diseases.<ref>{{cite web | title = AstraZeneca enters licensing agreements with LEO Pharma in skin diseases | date = July 2016 | url = https://www.astrazeneca.com/media-centre/press-releases/2016/astrazeneca-enters-licensing-agreements-with-leo-pharma-in-skin-diseases-01072016.html | access-date = 13 March 2017 | archive-date = 3 October 2021 | archive-url = https://web.archive.org/web/20211003152001/https://www.astrazeneca.com/media-centre/press-releases/2016/astrazeneca-enters-licensing-agreements-with-leo-pharma-in-skin-diseases-01072016.html | url-status = live }}</ref>

A phase IIb study of tralokinumab found that treatment was associated with early and sustained improvements in atopic dermatitis symptoms and tralokinumab had an acceptable safety and tolerability profile, thereby providing evidence for targeting IL-13 in patients with atopic dermatitis.<ref>{{cite journal | vauthors = Wollenberg A, Howell MD, Guttman-Yassky E, Silverberg JI, Kell C, Ranade K, Moate R, van der Merwe R | display-authors = 6 | title = Treatment of atopic dermatitis with tralokinumab, an anti-IL-13 mAb | journal = The Journal of Allergy and Clinical Immunology | volume = 143 | issue = 1 | pages = 135–141 | date = January 2019 | pmid = 29906525 | doi = 10.1016/j.jaci.2018.05.029 | doi-access = free | title-link=doi }}</ref>

In June 2017, [[Leo Pharma]] started phase III clinical trials with tralokinumab in atopic dermatitis.<ref>{{Cite press release|title = LEO Pharma starts phase 3 clinical study for tralokinumab in atopic dermatitis|url = https://www.leo-pharma.com/Home/LEO-Pharma/Media-centre/News/News-2017/LEO-Pharma-starts-phase-3-clinical-study-for-tralokinumab-in-atopic-dermatitis.aspx|website = LEO Pharma|date = 1 July 2016|access-date = 31 July 2019|archive-date = 31 July 2019|archive-url = https://web.archive.org/web/20190731160601/https://www.leo-pharma.com/Home/LEO-Pharma/Media-centre/News/News-2017/LEO-Pharma-starts-phase-3-clinical-study-for-tralokinumab-in-atopic-dermatitis.aspx|url-status = dead}}</ref>

== Society and culture ==

=== Legal status ===

In April 2021, the [[Committee for Medicinal Products for Human Use]] of the [[European Medicines Agency]] adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Adtralza, intended for the treatment of moderate‑to‑severe atopic dermatitis.<ref name="Adtralza: Pending EC decision">{{cite web | title=Adtralza: Pending EC decision | website=[[European Medicines Agency]] (EMA) | date=23 April 2021 | url=https://www.ema.europa.eu/en/medicines/human/summaries-opinion/adtralza | access-date=23 April 2021 | archive-date=23 April 2021 | archive-url=https://web.archive.org/web/20210423194118/https://www.ema.europa.eu/en/medicines/human/summaries-opinion/adtralza | url-status=live }}</ref> The applicant for this medicinal product is LEO Pharma A/S.<ref name="Adtralza: Pending EC decision" /> Tralokinumab was approved for medical use in the European Union in June 2021.<ref name="Adtralza EPAR" />

=== Names ===

Tralokinumab is the [[international nonproprietary name]] (INN)<ref>{{cite journal | vauthors=((World Health Organization)) | title=International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 64 | journal=WHO Drug Information | volume=24 | issue=3 | year=2010 | hdl=10665/74577 | hdl-access=free | author-link = World Health Organization }}</ref> and the [[United States Adopted Name]] (USAN).<ref>{{cite web|title=Statement On A Nonproprietary Name Adopted By The USAN Council: Tralokinumab|publisher=[[American Medical Association]]|url=https://searchusan.ama-assn.org/usan/documentDownload?uri=%2Funstructured%2Fbinary%2Fusan%2Ftralokinumab.pdf|access-date=4 July 2022|archive-date=30 December 2021|archive-url=https://web.archive.org/web/20211230033245/https://searchusan.ama-assn.org/usan/documentDownload?uri=%2Funstructured%2Fbinary%2Fusan%2Ftralokinumab.pdf|url-status=live}}</ref>

== References ==

{{Reflist}}

{{Other dermatological preparations}}

{{Monoclonals for immune system}}

{{Interleukin receptor modulators}}

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[[Category:Monoclonal antibodies]]

[[Category:Drugs developed by AstraZeneca]]

[[Category:Dermatologic drugs]]

[[Category:Immunomodulating drugs]]