Rezdiffra is indicated in conjunction with diet and exercise for the treatment of adults with noncirrhotic metabolic dysfunction-associated steatohepatitis (MASH) with moderate to advanced liver fibrosis (consistent with stages F2 to F3 fibrosis). This indication is approved under accelerated approval based on improvement of MASH and fibrosis. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. Limitation of Use: Avoid use in patients with decompensated cirrhosis.

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Rezdiffra works directly in the liver by stimulating THR-β to improve critical hepatic processes and reduce fibrosis1-3

A liver-directed treatment for noncirrhotic MASH and fibrosis1,4

1

THR-β signaling dysfunction worsens fibrosis progression4,5
THR-β signaling dysfunction worsens fibrosis progression
  • In MASH, impairment of THR-β signaling in the liver causes mitochondrial dysfunction, increased inflammation, and lipid buildup
  • This results in hepatocyte damage/death and fibrosis progression

2

Rezdiffra stimulates THR-β in the liver1,3,4
Rezdiffra selectively stimulates THR-β in the liver
  • Rezdiffra is a partial agonist of THR‑β, a nuclear receptor predominantly expressed in liver cells*
  • Rezdiffra stimulates THR-β signaling, regulating the expression of genes that improve critical processes in the liver, such as lipid metabolism and mitochondrial biogenesis

3

Improves metabolic function and reduces inflammation1-4
Improves metabolic function and reduces inflammation
  • Rezdiffra works to improve lipid metabolism (eg, reduces intrahepatic triglycerides and free fatty acids) and reduces inflammation in the liver
  • This helps to address drivers of disease progression, reduce liver damage, and improve liver health

A liver-directed treatment for noncirrhotic MASH and fibrosis1,4

1

THR-β signaling dysfunction worsens fibrosis progression4,5
  • In MASH, impairment of THR-β signaling in the liver causes mitochondrial dysfunction, increased inflammation, and lipid buildup
  • This results in hepatocyte damage/death and fibrosis progression

2

Rezdiffra stimulates THR-β in the liver1,3,4
  • Rezdiffra is a partial agonist of THR‑β, a nuclear receptor predominantly expressed in liver cells*
  • Rezdiffra stimulates THR-β signaling, regulating the expression of genes that improve critical processes in the liver, such as lipid metabolism and mitochondrial biogenesis

3

Improves metabolic function and reduces inflammation1-4
  • Rezdiffra works to improve lipid metabolism (eg, reduces intrahepatic triglycerides and free fatty acids) and reduces inflammation in the liver
  • This helps to address drivers of disease progression, reduce liver damage, and improve liver health
THR-β signaling dysfunction worsens fibrosis progression
Rezdiffra selectively stimulates THR-β in the liver
Improves metabolic function and reduces inflammation
*Actions of thyroid hormone outside the liver (including the heart and bones) are largely mediated through THR-α.1

Learn about oral, once-daily
dosing with Rezdiffra1

See Dosing
MASH=metabolic dysfunction-associated steatohepatitis, formerly known as NASH or nonalcoholic steatohepatitis; THR-α=thyroid hormone receptor alpha; THR-β=thyroid hormone receptor beta.
References:
  1. Rezdiffra. Prescribing Information. Madrigal Pharmaceuticals, Inc.
  2. Petta S et al. Liver International. 2024;44(7):1526-1536.
  3. Alonso-Merino E et al. Proc Natl Acad Sci. 2016;113(24):E3451-E3460.
  4. Karim G, Bansal MB. touchREV Endocrinol. 2023;19(1):60-70.
  5. Harrison SA et al. N Engl J Med. 2024;390(6):497-509.

IMPORTANT SAFETY INFORMATION AND INDICATION

EXPAND EXPAND

COLLAPSE COLLAPSE

WARNINGS AND PRECAUTIONS

Hepatotoxicity

Hepatotoxicity has been observed with the use of Rezdiffra. One patient developed substantial elevations of liver biochemistries that resolved when treatment was interrupted. Please see full Prescribing Information for more details on this specific case of Hepatotoxicity [see Warnings and Precautions (5.1)].

Monitor for elevations in liver tests, liver-related adverse reactions, and symptoms/signs of hepatotoxicity (eg, fatigue, nausea, vomiting, right upper quadrant pain or tenderness, jaundice, fever, rash, and/or eosinophilia [>5%]). If hepatotoxicity is suspected, discontinue Rezdiffra and monitor. If laboratory values return to baseline, weigh the potential risks against the benefits of restarting Rezdiffra. If laboratory values do not return to baseline, consider drug-induced autoimmune-like hepatitis (DI-ALH) or autoimmune liver disease in the evaluation of elevations in liver tests.

Gallbladder-Related Adverse Reactions

Cholelithiasis, acute cholecystitis, and obstructive pancreatitis (gallstone) were observed more often in Rezdiffra-treated patients than in placebo-treated patients. The exposure-adjusted incidence rates (EAIRs) for these events were less than 1 per 100 person-years (PY) for all treatment arms. If cholelithiasis is suspected, gallbladder diagnostic studies and appropriate clinical follow-up are indicated. If an acute gallbladder event is suspected, interrupt treatment until the event is resolved.

Drug Interaction with Certain Statins

An increase in exposure of atorvastatin, pravastatin, rosuvastatin and simvastatin was observed when concomitantly administered with Rezdiffra, which may increase the risk of adverse reactions related to these drugs.

Dosage adjustment for certain statins is recommended. Monitor for statin-related adverse reactions including, but not limited to, elevation of liver tests, myopathy, and rhabdomyolysis. Please see the upcoming Drug Interactions section of the Important Safety Information for more details.

ADVERSE REACTIONS

The most common adverse reactions with Rezdiffra (reported in ≥ 5% of patients and higher compared to placebo) are diarrhea, nausea, pruritus, vomiting, constipation, abdominal pain, and dizziness. Diarrhea and nausea were the most common causes of treatment discontinuation.

DRUG INTERACTIONS

Clinically Significant Interactions Affecting Rezdiffra

Clinically Significant Interactions Affecting Other Drugs

USE IN SPECIFIC POPULATIONS

Pregnancy

There are no available data on Rezdiffra use in pregnant women. Report pregnancies to Madrigal Pharmaceuticals, Inc.’s Adverse Event reporting line at 1-800-905-0324 and https://www.madrigalpharma.com/contact/.

Lactation

There is no information regarding the presence of Rezdiffra in human or animal milk, the effects on the breast-fed infant, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Rezdiffra and any potential adverse effects on the breastfed infant from Rezdiffra or from the underlying maternal condition.

Geriatric Use

Numerically higher incidence of adverse reactions have been observed in patients ≥65 years of age compared to younger adult patients.

Renal Impairment

Rezdiffra has not been studied in patients with severe renal impairment.

Hepatic Impairment

Avoid use in patients with decompensated cirrhosis (consistent with moderate to severe hepatic impairment). Moderate or severe hepatic impairment (Child-Pugh Class B or C) may increase the risk of adverse reactions.

The safety and effectiveness have not been established in patients with cirrhosis.

INDICATION

Rezdiffra is indicated in conjunction with diet and exercise for the treatment of adults with noncirrhotic metabolic dysfunction-associated steatohepatitis (MASH) with moderate to advanced liver fibrosis (consistent with stages F2 to F3 fibrosis).

This indication is approved under accelerated approval based on improvement of MASH and fibrosis. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

Limitation of Use: Avoid use in patients with decompensated cirrhosis.

Please see full Prescribing Information for Rezdiffra.

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