resmetirom
{{Short description|Chemical compound}}
{{Use dmy dates|date=March 2024}}
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{{Infobox drug
| image = Resmetirom.svg
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| pronounce =
| tradename = Rezdiffra
| Drugs.com = {{drugs.com|monograph|resmetirom}}
| MedlinePlus =
| DailyMedID = Resmetirom
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| routes_of_administration = By mouth
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| ATC_prefix = None
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| legal_US = Rx-only
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| CAS_number = 920509-32-6
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| PubChem = 15981237
| IUPHAR_ligand =
| DrugBank = DB12914
| ChemSpiderID =
| UNII = RE0V0T1ES0
| KEGG = D11602
| ChEBI =
| ChEMBL = 3261331
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| PDB_ligand =
| synonyms = MGL-3196
| IUPAC_name = 2-[3,5-dichloro-4-[(6-oxo-5-propan-2-yl-1H-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
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Resmetirom, sold under the brand name Rezdiffra, is a medication used for the treatment of noncirrhotic nonalcoholic steatohepatitis. It is a thyroid hormone receptor beta (NR1A2) agonist.
The most common side effects include diarrhea and nausea.
Resmetirom was approved for medical use in the United States in March 2024.{{cite press release | title=FDA Approves First Treatment for Patients with Liver Scarring Due to Fatty Liver Disease | website=U.S. Food and Drug Administration (FDA) | 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}}{{cite web | title=Novel Drug Approvals for 2024 | website=U.S. Food and Drug Administration (FDA) | date=29 April 2024 | url=https://www.fda.gov/drugs/novel-drug-approvals-fda/novel-drug-approvals-2024 | access-date=30 April 2024 | archive-date=30 April 2024 | archive-url=https://web.archive.org/web/20240430031024/https://www.fda.gov/drugs/novel-drug-approvals-fda/novel-drug-approvals-2024 | url-status=live }}{{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=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 }} The US Food and Drug Administration (FDA) considers it to be a first-in-class medication.{{cite report | title=New Drug Therapy Approvals 2024 | website=U.S. Food and Drug Administration (FDA) | 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 }}
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).
History
In a phase III clinical trial, it was found to be effective for resolving noncirrhotic nonalcoholic steatohepatitis and improving liver fibrosis.{{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 }}
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. The surrogate endpoint measured the extent of liver inflammation and scarring. 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. 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.
The FDA granted the application for resmetirom accelerated approval, along with breakthrough therapy, fast track, and priority review designations. The FDA granted the approval of Rezdiffra to Madrigal Pharmaceuticals.
Research
In 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).{{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 }}
References
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{{Bile and liver therapy}}
{{Thyroid hormone receptor modulators}}
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