Eltrombopag

Eltrombopag was approved by the US Food and Drug Administration (FDA) in November 2008, for the treatment of thrombocytopenia in people with chronic immune (idiopathic) thrombocytopenic purpura who have had an insufficient response to corticosteroids, immunoglobulin therapy, or splenectomy.{{cite web|title=Approval Letter|url=http://www.accessdata.fda.gov/drugsatfda_docs/appletter/2008/022291s000ltr.pdf|publisher=U.S. Food and Drug Administration (FDA)|access-date=18 March 2016|archive-date=28 February 2017|archive-url=https://web.archive.org/web/20170228134225/http://www.accessdata.fda.gov/drugsatfda_docs/appletter/2008/022291s000ltr.pdf|url-status=live}}{{cite web | title=Drug Approval Package: Promacta (Eltrombopag) NDA #022291 | publisher=U.S. Food and Drug Administration (FDA) | date=14 January 2009 | url=https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/022291s000_TOC.cfm | access-date=22 May 2021 | archive-date=3 April 2021 | archive-url=https://web.archive.org/web/20210403054745/https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/022291s000_TOC.cfm | url-status=live }}{{cite web | title=Summary Review | publisher=U.S. Food and Drug Administration (FDA) | date=19 January 2008 | url=https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/022291s000_SumR.pdf | access-date=22 May 2021 | archive-date=23 May 2021 | archive-url=https://web.archive.org/web/20210523051334/https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/022291s000_SumR.pdf | url-status=live }}

In August 2015, the FDA approved eltrombopag (Promacta for oral suspension) for the treatment of thrombocytopenia in children one year of age and older with idiopathic thrombocytopenia who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy.{{cite press release|title=FDA extends use of Promacta in young children with rare blood disorder|url=https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm459430.htm|publisher=U.S. Food and Drug Administration (FDA)|access-date=18 March 2016|archive-date=26 January 2018|archive-url=https://web.archive.org/web/20180126103132/https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm459430.htm|url-status=dead}} {{PD-notice}}

In preclinical studies, the compound was shown to interact selectively with the thrombopoietin receptor, leading to activation of the JAK-STAT signaling pathway and increased proliferation and differentiation of megakaryocytes. Animal studies confirmed that it increased platelet counts. In 73 healthy volunteers, higher doses of eltrombopag caused larger increases in the number of circulating platelets without tolerability problems.{{cite journal | vauthors = Jenkins JM, Williams D, Deng Y, Uhl J, Kitchen V, Collins D, Erickson-Miller CL | title = Phase 1 clinical study of eltrombopag, an oral, nonpeptide thrombopoietin receptor agonist | journal = Blood | volume = 109 | issue = 11 | pages = 4739–4741 | date = June 2007 | pmid = 17327409 | doi = 10.1182/blood-2006-11-057968 | title-link = doi | doi-access = free }}

Eltrombopag has been shown to be effective in two major clinical syndromes: idiopathic thrombocytopenic purpura (ITP){{cite journal | vauthors = Bussel JB, Cheng G, Saleh MN, Psaila B, Kovaleva L, Meddeb B, Kloczko J, Hassani H, Mayer B, Stone NL, Arning M, Provan D, Jenkins JM | title = Eltrombopag for the treatment of chronic idiopathic thrombocytopenic purpura | journal = The New England Journal of Medicine | volume = 357 | issue = 22 | pages = 2237–2247 | date = November 2007 | pmid = 18046028 | doi = 10.1056/NEJMoa073275 | doi-access = free }} and cirrhosis due to hepatitis C (in which low platelet counts may be a contraindication for interferon treatment).{{cite journal | vauthors = McHutchison JG, Dusheiko G, Shiffman ML, Rodriguez-Torres M, Sigal S, Bourliere M, Berg T, Gordon SC, Campbell FM, Theodore D, Blackman N, Jenkins J, Afdhal NH | title = Eltrombopag for thrombocytopenia in patients with cirrhosis associated with hepatitis C | journal = The New England Journal of Medicine | volume = 357 | issue = 22 | pages = 2227–2236 | date = November 2007 | pmid = 18046027 | doi = 10.1056/NEJMoa073255 | url = https://scholarscompass.vcu.edu/cgi/viewcontent.cgi?article=1013&context=vcuhealth_pubs | access-date = 12 December 2019 | url-status = live | doi-access = free | archive-url = https://web.archive.org/web/20211017000257/https://scholarscompass.vcu.edu/cgi/viewcontent.cgi?article=1013&context=vcuhealth_pubs | archive-date = 17 October 2021 }}

After six weeks of therapy in a phase III trial, eltrombopag 50 mg/day was associated with a significantly higher response rate than placebo in adult patients with chronic idiopathic thrombocytopenic purpura (ITP).{{cite journal | vauthors = Garnock-Jones KP, Keam SJ | title = Eltrombopag | journal = Drugs | volume = 69 | issue = 5 | pages = 567–576 | year = 2009 | pmid = 19368418 | doi = 10.2165/00003495-200969050-00005 | s2cid = 265943270 }}

Eltrombopag received breakthrough therapy designation from the US Food and Drug Administration (FDA) in February 2014, for people with aplastic anemia for which immunosuppression has not been successful.{{cite web|title=Eltrombopag / Promacta|url=https://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm459467.htm|publisher=U.S. Food and Drug Administration (FDA)|access-date=18 March 2016|archive-date=6 December 2016|archive-url=https://web.archive.org/web/20161206124948/http://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm459467.htm|url-status=live}} In 2017, the NIH made Eltrombopag a standard of care in aplastic anemia.{{cite journal | vauthors = Townsley DM, Scheinberg P, Winkler T, Desmond R, Dumitriu B, Rios O, Weinstein B, Valdez J, Lotter J, Feng X, Desierto M, Leuva H, Bevans M, Wu C, Larochelle A, Calvo KR, Dunbar CE, Young NS | title = Eltrombopag Added to Standard Immunosuppression for Aplastic Anemia | journal = The New England Journal of Medicine | volume = 376 | issue = 16 | pages = 1540–1550 | date = April 2017 | pmid = 28423296 | pmc = 5548296 | doi = 10.1056/NEJMoa1613878 | title-link = doi | doi-access = free }}

In October 2024, 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 Eltrombopag Viatris, intended for the treatment of people with primary immune thrombocytopenia (ITP) and thrombocytopenia associated with chronic hepatitis C. The applicant for this medicinal product is Viatris Limited.{{cite web | title=Eltrombopag Viatris EPAR | website=European Medicines Agency (EMA) | date=17 October 2024 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/eltrombopag-viatris | access-date=19 October 2024}}Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged. Eltrombopag Viatris was authorized in December 2024.{{cite web | title=Eltrombopag Viatris Product information | website=Union Register of medicinal products | date=13 December 2024 | url=https://ec.europa.eu/health/documents/community-register/html/h1869.htm | access-date=17 December 2024}}

It has been shown to produce a trilineage hematopoiesis in some people with aplastic anemia, resulting in increased platelet counts, along with red and white blood cell counts.{{cite journal | vauthors = Desmond R, Townsley DM, Dumitriu B, Olnes MJ, Scheinberg P, Bevans M, Parikh AR, Broder K, Calvo KR, Wu CO, Young NS, Dunbar CE | display-authors = 6 | title = Eltrombopag restores trilineage hematopoiesis in refractory severe aplastic anemia that can be sustained on discontinuation of drug | journal = Blood | volume = 123 | issue = 12 | pages = 1818–1825 | date = March 2014 | pmid = 24345753 | pmc = 3962161 | doi = 10.1182/blood-2013-10-534743 }} Eltrombopag has been shown to target ELAVL1/HuR-RNA interactions affecting gene expression, iron metabolism, and glycoprotein hormones, alpha polypeptide (CGA) levels.{{cite journal | vauthors = Idlin N, Krishnamoorthy S, Wolczyk M, Fakhri M, Lechowski M, Stec N, Milek J, Mandal PK, Cendrowski J, Spanos C, Dziembowska M, Mleczko-Sanecka K, Rappsilber J, Michlewski G | display-authors = 6 | title = Effects of genetic ablation and pharmacological inhibition of HuR on gene expression, iron metabolism, and hormone levels | journal = BMC Biology | volume = 23 | issue = 1 | pages = 24 | date = January 2025 | pmid = 39849491 | pmc = 11756078 | doi = 10.1186/s12915-025-02131-z | doi-access = free }} The transcription factor EB (TFEB) has been detected as an Eltrombopag target in starvation-induced conditions. {{cite journal | vauthors = Lin Y, Shi Q, Yang G, Shi F, Zhou Y, Wang T, Xu P, Li P, Liu Z, Sun H, Zhao Z, Ding K, Wang Z, Feng H, Yu B, Fang P, Wang J | display-authors = 6 | title = A small-molecule drug inhibits autophagy gene expression through the central regulator TFEB | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 120 | issue = 7 | pages = e2213670120 | date = February 2023 | pmid = 36749723 | pmc = 9963785 | doi = 10.1073/pnas.2213670120 | doi-access = free | bibcode = 2023PNAS..12013670L }}

{{reflist}}

• {{ClinicalTrialsGov|NCT00102739|SB-497115 (Oral Thrombopoietin Receptor Agonist) Versus Placebo In Adults With Refractory Immune Thrombocytopenic Purpura (ITP)}}
• {{ClinicalTrialsGov|NCT00370331|RAISE: Randomized Placebo-Controlled Idiopathic Thrombocytopenic Purpura (ITP) Study With Eltrombopag (RAISE)}}
• {{ClinicalTrialsGov|NCT00351468|EXTEND (Eltrombopag Extended Dosing Study) (EXTEND)}}
• {{ClinicalTrialsGov|NCT01520909|Study of a New Medication for Childhood Chronic Immune Thrombocytopenia (ITP), a Blood Disorder of Low Platelet Counts That Can Lead to Bruising Easily, Bleeding Gums, and/or Bleeding Inside the Body. (PETIT2)}}
• {{ClinicalTrialsGov|NCT00908037|Efficacy and Safety Study of Eltrombopag in Pediatric Patients With Thrombocytopenia From Chronic Idiopathic Thrombocytopenic Purpura (ITP) (PETIT)}}
• {{ClinicalTrialsGov|NCT00516321|Eltrombopag To Initiate And Maintain Interferon Antiviral Treatment To Subjects With Hepatitis C Related Liver Disease}}
• {{ClinicalTrialsGov|NCT00529568|Eltrombopag To Initiate And Maintain Interferon Antiviral Treatment To Benefit Subjects With Hepatitis C Liver Disease}}
• {{ClinicalTrialsGov|NCT01623167|Eltrombopag With Standard Immunosuppression for Severe Aplastic Anemia}}
• {{ClinicalTrialsGov|NCT00922883|A Pilot Study of the Thrombopoietin-Receptor Agonist Eltrombopag in Refractory Aplastic Anemia Patients}}

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Category:Biphenyls

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Category:Thrombopoietin receptor agonists