Resmetirom

Resmetirom, sold under the brand name Rezdiffra, is a medication used for the treatment of noncirrhotic nonalcoholic steatohepatitis.^[1] It is a thyroid hormone receptor beta (NR1A2) agonist.^[1]

Resmetirom

Clinical data
Trade names	Rezdiffra, Resiliva
Other names	MGL-3196
AHFS/Drugs.com	Monograph
License data	US DailyMed: Resmetirom
Routes of administration	By mouth
ATC code	None
Legal status
Legal status	US: ℞-only[1]
Identifiers
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
CAS Number	920509-32-6
PubChem CID	15981237
DrugBank	DB12914
UNII	RE0V0T1ES0
KEGG	D11602
ChEMBL	ChEMBL3261331
CompTox Dashboard (EPA)	DTXSID601352610
Chemical and physical data
Formula	C17H12Cl2N6O4
Molar mass	435.22 g·mol−1
3D model (JSmol)	Interactive image
SMILES CC(C)C1=CC(=NNC1=O)OC2=C(C=C(C=C2Cl)N3C(=O)NC(=O)C(=N3)C#N)Cl
InChI InChI=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) Key:FDBYIYFVSAHJLY-UHFFFAOYSA-N

The most common side effects include diarrhea and nausea.^[2]

Resmetirom was approved for medical use in the United States in March 2024.^[2][3][4] The US Food and Drug Administration (FDA) considers it to be a first-in-class medication.^[5]

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).^[1][2]

History

In a phase III clinical trial, it was found to be effective for resolving noncirrhotic nonalcoholic steatohepatitis and improving liver fibrosis.^[6]

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.^[2] The surrogate endpoint measured the extent of liver inflammation and scarring.^[2] 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.^[2] 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.^[2]

The FDA granted the application for resmetirom accelerated approval, along with breakthrough therapy, fast track, and priority review designations.^[2] The FDA granted the approval of Rezdiffra to Madrigal Pharmaceuticals.^[2]. First generic version was manufactured by Everest Pharmaceuticals Limited under the brand name "Resiliva".

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).^[7]