Rezdiffra (Resmetirom) for NASH Treatment
Yes, you are correct—Rezdiffra (resmetirom) is the first FDA-approved medication specifically for NASH, receiving accelerated approval in March 2024 for adults with non-cirrhotic NASH and moderate-to-advanced liver fibrosis (F2-F3 stages). 1, 2
FDA-Approved Indication
Rezdiffra is approved for use in conjunction with diet and exercise for the treatment of adults with non-cirrhotic NASH with moderate-to-advanced liver fibrosis consistent with stages F2 to F3 fibrosis. 2, 3
Mechanism and Efficacy
Resmetirom is an oral thyroid hormone receptor-β (THR-β) agonist that targets the underlying metabolic causes of NASH. 2
In clinical trial NCT03900429, resmetirom (80 or 100 mg daily) demonstrated effective improvement in fibrosis by at least one stage without worsening of NAFLD activity score (NAS), as well as improvement in lipid profile of NASH patients. 1
The drug achieved NASH resolution in a significantly higher proportion of patients compared to placebo in biopsy-proven NASH. 1
Clinical Context and Treatment Algorithm
For patients with biopsy-proven NASH and F2-F3 fibrosis:
Implement lifestyle modifications targeting 7-10% weight loss through caloric restriction and exercise as the foundation of treatment. 4, 5
Add Rezdiffra as pharmacologic therapy specifically for patients with biopsy-confirmed non-cirrhotic NASH with F2-F3 fibrosis. 1, 2
Continue aggressive management of metabolic comorbidities including diabetes, dyslipidemia, and hypertension. 4, 6
For patients without biopsy confirmation or with F0-F1 fibrosis:
Focus solely on lifestyle modifications without pharmacotherapy, as these patients have excellent prognosis from a liver standpoint. 4
Consider vitamin E (800 IU daily) or pioglitazone (30 mg daily) in appropriate candidates with biopsy-proven NASH without cirrhosis. 4
Important Caveats
Rezdiffra received accelerated approval, meaning continued approval is contingent on verification of clinical benefit in confirmatory trials. 2
The drug is specifically indicated for non-cirrhotic NASH—it should not be used in patients with decompensated cirrhosis or cirrhotic NASH. 2, 3
Pharmacological treatment should be limited to patients with biopsy-proven NASH and fibrosis ≥F2, as this stage is an independent predictor of liver-related complications. 5
Prior to Rezdiffra's approval, the 2021 guidelines noted that no drugs under development had met efficacy targets in more than 50% of patients, and the FDA had rejected conditional approval of obeticholic acid due to severe itching and increased cardiovascular risk. 7
Monitoring Requirements
Perform right upper quadrant ultrasound with or without serum AFP every 6 months for HCC surveillance in patients with advanced fibrosis (F3). 4, 5
Monitor with repeated non-invasive tests including FIB-4 and liver stiffness measurement every 6 months for intermediate and high-risk patients. 5
Continue lifelong HCC surveillance even after metabolic improvement. 4