{{Short description|Chemical compound}} {{Use dmy dates|date=March 2024}} {{cs1 config |name-list-style=vanc |display-authors=3}} {{Infobox drug | image = Resmetirom.svg | image_class = skin-invert-image | alt = | caption =
<!-- Clinical data --> | pronounce = | tradename = Rezdiffra | Drugs.com = {{drugs.com|monograph|resmetirom}} | MedlinePlus = a624021 | DailyMedID = Resmetirom | pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X --> | pregnancy_AU_comment = | pregnancy_category= | routes_of_administration = By mouth | class = | ATC_prefix = A05 | ATC_suffix = BA11 | 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 = <!-- OTC, Rx-only, Schedule I, II, III, IV, V, VI, VII, VIII --> | legal_CA_comment = | legal_DE = <!-- Anlage I, II, III or Unscheduled --> | legal_DE_comment = | legal_NZ = <!-- Class A, B, C --> | legal_NZ_comment = | legal_UK = <!-- GSL, P, POM, CD, CD Lic, CD POM, CD No Reg POM, CD (Benz) POM, CD (Anab) POM or CD Inv POM / Class A, B, C --> | legal_UK_comment = | legal_US = Rx-only | legal_US_comment = <ref name= "Rezdiffra FDA label">{{cite web | title= Rezdiffra- resmetirom tablet, coated; Rezdiffra- resmetirom tablet, coated; Rezdiffra- resmetirom tablet, coated | website=DailyMed| publisher = National Institutes of Health | location = US | date=14 March 2024 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=e67ea09f-a840-439c-86c8-f98585f978b2 | access-date=2 April 2024 | archive-date=2 April 2024 | archive-url=https://web.archive.org/web/20240402061748/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=e67ea09f-a840-439c-86c8-f98585f978b2 | url-status=live }}</ref> | legal_EU = Rx-only | legal_EU_comment = <ref name="Rezdiffra EPAR" /><ref name="Rezdiffra PI" /> | legal_UN = <!-- N I, II, III, IV / P I, II, III, IV --> | legal_UN_comment = | legal_status = <!-- For countries not listed above -->
<!-- Pharmacokinetic data --> | bioavailability = | protein_bound = | metabolism = | metabolites = | onset = | elimination_half-life = | duration_of_action = | excretion =
<!-- Identifiers --> | CAS_number = 920509-32-6 | CAS_supplemental = | PubChem = 15981237 | IUPHAR_ligand = | DrugBank = DB12914 | ChemSpiderID = | UNII = RE0V0T1ES0 | KEGG = D11602 | ChEBI = | ChEMBL = 3261331 | NIAID_ChemDB = | PDB_ligand = | synonyms = MGL-3196
<!-- Chemical and physical data --> | IUPAC_name = 2-[3,5-dichloro-4-[(6-oxo-5-propan-2-yl-1''H''-pyridazin-3-yl)oxy]phenyl]-3,5-dioxo-1,2,4-triazine-6-carbonitrile | SMILES = CC(C)C1=CC(=NNC1=O)OC2=C(C=C(C=C2Cl)N3C(=O)NC(=O)C(=N3)C#N)Cl | C = 17 | H = 12 | Cl = 2 | N = 6 | O = 4 | StdInChI = 1S/C17H12Cl2N6O4/c1-7(2)9-5-13(22-23-15(9)26)29-14-10(18)3-8(4-11(14)19)25-17(28)21-16(27)12(6-20)24-25/h3-5,7H,1-2H3,(H,23,26)(H,21,27,28) | StdInChI_comment = | StdInChIKey = FDBYIYFVSAHJLY-UHFFFAOYSA-N | density = | density_notes = | melting_point = | melting_high = | melting_notes = | boiling_point = | boiling_notes = | solubility = | sol_units = | specific_rotation = }}
'''Resmetirom''', sold under the brand name '''Rezdiffra''', is a medication used to treat a form of fatty liver disease. Specifically it is used in the treatment of noncirrhotic metabolic dysfunction associated steatohepatitis (MASH) (formerly known as nonalcoholic steatohepatitis NASH).<ref name="Rezdiffra FDA label" /> It is structurally similar to the thyroid hormone triiodothyronine and acts as an agonist of the thyroid hormone receptor beta (NR1A2).<ref name="Rezdiffra FDA label" />
The most common side effects include diarrhea and nausea.<ref name="FDA 20240314" />
Resmetirom was approved for medical use in the US in March 2024,<ref name="FDA 20240314">{{cite press release | title=FDA Approves First Treatment for Patients with Liver Scarring Due to Fatty Liver Disease | website= FDA.gov| publisher =Food and Drug Administration | location = US| date=14 March 2024 | url=https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-patients-liver-scarring-due-fatty-liver-disease | access-date=14 March 2024 | archive-date=14 March 2024 | archive-url=https://web.archive.org/web/20240314232316/https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-patients-liver-scarring-due-fatty-liver-disease | url-status=live }} {{PD-notice}}</ref> and in the European Union in August 2025.<ref name= "Rezdiffra PI" /> The US Food and Drug Administration considers it to be a first-in-class medication.<ref>{{cite report | title=New Drug Therapy Approvals 2024 | website= FDA.gov| publisher = Food and Drug Administration | location = US| date= January 2025 | url=https://www.fda.gov/media/184967/download | format=PDF | access-date=21 January 2025 | archive-url=https://web.archive.org/web/20250121045744/https://www.fda.gov/media/184967/download | archive-date=21 January 2025 | url-status=live }}</ref>
== Medical uses == Resmetirom is indicated, in conjunction with diet and exercise, for the treatment of adults with noncirrhotic nonalcoholic steatohepatitis with moderate to advanced liver fibrosis (consistent with stages F2 to F3 fibrosis).<ref name="Rezdiffra FDA label" /><ref name="FDA 20240314" />
== History == In a phase III clinical trial, it was found to be effective for resolving noncirrhotic nonalcoholic steatohepatitis and improving liver fibrosis.<ref>{{cite journal | vauthors = Harrison SA, Bedossa P, Guy CD, Schattenberg JM, Loomba R, Taub R, Labriola D, Moussa SE, Neff GW, Rinella ME, Anstee QM, Abdelmalek MF, Younossi Z, Baum SJ, Francque S, Charlton MR, Newsome PN, Lanthier N, Schiefke I, Mangia A, Pericàs JM, Patil R, Sanyal AJ, Noureddin M, Bansal MB, Alkhouri N, Castera L, Rudraraju M, Ratziu V | title = A Phase 3, Randomized, Controlled Trial of Resmetirom in NASH with Liver Fibrosis | journal = The New England Journal of Medicine | volume = 390 | issue = 6 | pages = 497–509 | date = February 2024 | pmid = 38324483 | doi = 10.1056/NEJMoa2309000 | s2cid = 267544939 | hdl = 11573/1706995 | hdl-access = free }}</ref>
The US Food and Drug Administration (FDA) evaluated the safety and efficacy of resmetirom based on an analysis of a surrogate endpoint at month twelve in a 54-month, randomized, double-blind placebo-controlled trial.<ref name="FDA 20240314" /> The surrogate endpoint measured the extent of liver inflammation and scarring.<ref name="FDA 20240314" /> The FDA requires the sponsor to conduct a postapproval study to verify and describe the clinical benefit of resmetirom, which will be done through completing the same 54-month study.<ref name="FDA 20240314" /> In the trial, 888 participants were randomly assigned to receive one of the following: placebo (294 participants); 80 milligrams of resmetirom (298 participants); or 100 milligrams of resmetirom (296 participants); once daily, in addition to standard care for noncirrhotic nonalcoholic steatohepatitis, which includes counseling for healthy diet and exercise.<ref name="FDA 20240314" />
The FDA granted the application for resmetirom accelerated approval, along with breakthrough therapy, fast track, and priority review designations.<ref name="FDA 20240314" /> The FDA granted the approval of Rezdiffra to Madrigal Pharmaceuticals.<ref name="FDA 20240314" />
== Society and culture == === Legal status === Resmetirom was approved for medical use in the US in March 2024.<ref>{{cite press release | title= Madrigal Pharmaceuticals Announces FDA Approval of Rezdiffra (resmetirom) for the Treatment of Patients with Noncirrhotic Nonalcoholic Steatohepatitis (NASH) with Moderate to Advanced Liver Fibrosis | website= madrigalpharma.com | publisher= Madrigal Pharmaceuticals | date=14 March 2024 | url=https://ir.madrigalpharma.com/news-releases/news-release-details/madrigal-pharmaceuticals-announces-fda-approval-rezdiffratm | access-date=14 March 2024 | archive-date=14 March 2024 | archive-url=https://web.archive.org/web/20240314230444/https://ir.madrigalpharma.com/news-releases/news-release-details/madrigal-pharmaceuticals-announces-fda-approval-rezdiffratm | url-status=live }}</ref>
In June 2025, the Committee for Medicinal Products for Human Use of the European Medicines Agency adopted a positive opinion, recommending the granting of a conditional marketing authorization for the medicinal product Rezdiffra, intended for the treatment of adults with noncirrhotic metabolic dysfunction-associated steatohepatitis (MASH).<ref name="Rezdiffra EPAR" /> The applicant for this medicinal product is Madrigal Pharmaceuticals EU Limited.<ref name="Rezdiffra EPAR">{{cite web | title=Rezdiffra EPAR | website= ema.europa.eu | publisher= European Medicines Agency| date=20 June 2025 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/rezdiffra | access-date=26 June 2025}} Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.</ref><ref>{{cite press release | title=First treatment against liver scarring caused by a type of 'fatty liver disease' | website= ema.europa.eu | publisher= European Medicines Agency| date=20 June 2025 | url=https://www.ema.europa.eu/en/news/first-treatment-against-liver-scarring-caused-type-fatty-liver-disease | access-date=26 June 2025}}</ref> Resmetirom was authorized for medical use in the European Union in August 2025.<ref name="Rezdiffra EPAR" /><ref name="Rezdiffra PI">{{cite web | title=Rezdiffra PI | via= ec.europa.eu| website= Union Register of Medicinal Products | date=19 August 2025 | url=https://ec.europa.eu/health/documents/community-register/html/h1962.htm | access-date=18 September 2025}}</ref>
== Research == A systematic review and meta-analysis of resmetirom, published in 2024, found that it is well tolerated and that it improves hepatic fat content, liver enzymes, and fibrosis biomarkers in people with non-alcoholic steatohepatitis (NASH).<ref>{{cite journal | vauthors = Dutta D, Kamrul-Hasan AB, Mondal E, Nagendra L, Joshi A, Bhattacharya S | title = Role of Resmetirom, a Liver-Directed, Thyroid Hormone Receptor Beta-Selective Agonist, in Managing Nonalcoholic Steatohepatitis: A Systematic Review and Meta-Analysis | journal = Endocrine Practice | volume = 30 | issue = 7 | pages = 631–638 | date = July 2024 | pmid = 38697306 | doi = 10.1016/j.eprac.2024.04.016 }}</ref>
== References == {{reflist}}
{{Bile and liver therapy}} {{Thyroid hormone receptor modulators}} {{Portal bar | Medicine}} {{Authority control}}
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