Healthful Living Rx: MASH Clinical Perspectives

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IMPROVING FIBROSIS & MASH is no longer wishful thinking  Rezdira is the first and only treatment for MASH with moderate to advanced fibrosis that activates THR-β directly in the liver 1 For adults with noncirrhotic MASH with moderate to advanced fibrosis, in conjunction with diet and exercise. 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.

Oral, Once- Daily Dosing 1

Dual E icacy 1

Demonstrated Safety 1

Liver- Directed 1

At Week 52, Rezdi‚ra delivers statistically significant fibrosis improvement* with no worsening of steatohepatitis and steatohepatitis resolution † with no worsening of fibrosis. 1

MASH=metabolic dysfunction-associated steatohepatitis.

IMPORTANT SAFETY INFORMATION ‘cont.’

Renal Impairment The recommended dosage of Rezdi‚ra in patients with mild, moderate, or severe renal impairment is the same as in patients with normal kidney function. 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 e‚ectiveness of Rezdi‚ra have not been established in patients with cirrhosis. Trial design: MAESTRO-NASH is an ongoing pivotal Phase 3, multicenter, randomized, double-blind, placebo-controlled trial in 888 patients with biopsy- confirmed MASH with liver fibrosis (F2 or F3). Patients were randomized 1:1:1 to Rezdi‚ra (80 mg or 100 mg) or placebo to evaluate the e‚icacy and safety at 52 weeks. 1,2 *Fibrosis improvement: ≥1-stage improvement in fibrosis with no worsening of steatohepatitis (defined as no increase in score for ballooning, inflammation, or steatosis). 1 † Steatohepatitis resolution: Resolution of steatohepatitis (score of 0-1 for inflammation, 0 for ballooning, and any value for steatosis) with no worsening of fibrosis. 1

Clinically Significant Interactions Aecting Other Drugs • Statins: Limit daily rosuvastatin and simvastatin dosage to 20 mg. Limit pravastatin and atorvastatin dosage to 40 mg. • CYP2C8 Substrates: Monitor patients more frequently for substrate-related adverse reactions if Rezdi‚ra is co-administered with CYP2C8 substrates where minimal concentration changes may lead to serious adverse reactions. USE IN SPECIFIC POPULATIONS Pregnancy There are no available data on Rezdi‚ra use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. Report pregnancies to Madrigal Pharmaceuticals, Inc. Adverse Event Reporting line at 1-800-905-0324 and visit https://pregnancyregistry.madrigalpharma.com for information about a pregnancy safety study. Lactation There is no information regarding the presence of Rezdi‚ra in human or animal milk, the e‚ects on the breast-fed infant, or the e‚ects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Rezdi‚ra and any potential adverse e‚ects on the breastfed infant from Rezdi‚ra 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.

THR- β =thyroid hormone receptor beta. References: 1. Rezdi‚ra. Prescribing Information. Madrigal Pharmaceuticals, Inc. 2. Harrison SA et al. N Engl J Med. 2024;390(6):497-509.

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US-PP-RES-00716-v3 02/26

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