REZDIFFRA (resmetiron)

REZDIFFRA (resmetirom)

Self-Administration – oral tablets

Diagnosis considered for coverage:

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

Coverage Criteria:

For diagnosis of NASH:

• Diagnosis of metabolic dysfunction-associated steatohepatitis (MASH), formerly known as nonalcoholic steatohepatitis (NASH); AND
• Patient does not have cirrhosis (e.g., decompensated cirrhosis); AND
• Submission of medical records (e.g., chart notes) confirming diagnosis has been confirmed by one of the following: 
  • FibroScan-aspartate aminotransferase (FAST) 
  • MRI-aspartate aminotransferase (MAST) 
  • Liver biopsy; AND
• Submission of medical records (e.g., chart notes) confirming disease is fibrosis stage F2 or F3 as confirmed by one of the following: 
  • FibroScan 
  • Fibrosis-4 index (FIB-4) 
  • Magnetic Resonance Elastography (MRE); AND
• Presence of greater than or equal to 3 metabolic risk factors (e.g., Type 2 diabetes, hypertension, obesity); AND
• Submission of medical records (e.g., chart notes) confirming drug is used as an adjunct to lifestyle modification (e.g., dietary or caloric restriction, exercise, behavioral support, community-based program); AND
• Prescribed by or in consultation with a gastroenterologist or hepatologist

Reauthorization Criteria:

For diagnosis of NASH:

• Patient demonstrates positive response to therapy (e.g., NASH resolution, fibrosis stage improvement, etc.); AND
• Submission of medical records (e.g., chart notes) confirming drug will continue to be used as an adjunct to lifestyle modification (e.g., dietary or caloric restriction, exercise, behavioral support, community-based program)

Coverage Duration: 

• Initial: 1 year
• Reauthorization: 1 year

Dosing:

For diagnosis of NASH:

• The recommended dosage of REZDIFFRA is based on actual body weight. For patients weighing:
  • <100 kg, the recommended dosage is 80 mg orally once daily
  • ≥100 kg, the recommended dosage is 100 mg orally once daily
• Dose reduction by 20 mg/day recommended with concomitant moderate CYP2C8 inhibitors (e.g., clopidogrel)

Authorization is not covered for the following:

• The use of this drug for indications not listed in this policy does not meet the coverage criteria established by the Western Health Advantage (WHA) Pharmacy and Therapeutics (P&T) Committee.

Additional Information: 

• Aside from Rezdiffra (resmetirom), there are no other FDA-approved treatments for NASH (or any other subset of NAFLD)
• Treatment options currently target weight reduction and comorbid disease management

Policy Updates:

• 09/01/2024 – New policy for Rezdiffra approved by WHA P&T Committee. (P&T, 08/20/2024)

References:

1. Rinella ME, Neuschwander-Tetri BA, Siddiqui MS, et al. AASLD practice guidance on the clinical assessment and management of nonalcoholic fatty liver disease. 
2. Rezdiffra Prescribing Information. Madrigal Pharmaceuticals. West Conshohocken, PA. March 2024. 
3. Harrison SA, Bedossa P, Guy CD, et al. A Phase 3, Randomized, Controlled Trial of Resmetirom in NASH with Liver Fibrosis. The New England Journal of Medicine. 2024;390(6):497-509.