CurrentCentenePolicy CP PHAR.647

Resmetirom (Rezdiffra)

Clinical policy defining medical necessity criteria, initial and continued therapy requirements, dosing, exclusions, and duration for resmetirom (Rezdiffra) for adults with noncirrhotic metabolic dysfunction-associated steatohepatitis (MASH; formerly NASH) with stage F2-F3 fibrosis across Commercial, HIM, and Medicaid lines of business.

Policy Summary

PayerCentene

PolicyResmetirom (Rezdiffra)

Policy CodePolicy CP PHAR.647

Change TypeRevised (FDA labeling update; 4Q2024 annual review)

Effective Date03.14.24

Next Review Date

Key ActionProvider must submit documentation (chart notes, labs, imaging or biopsy) showing fibrosis confirmation within last 6 months and lifestyle modification documentation for BMI >= 25 kg/m2 when requesting coverage.

POLICY UPDATE CHANGES

Updated policy to reflect FDA labeling: added MASH terminology, expanded diagnostic test options and 6-month timeframe, lowered BMI threshold for lifestyle documentation from 27 to 25, required prescriber attestation for standard of care, updated FDA-labeled dosing, and added MASH resolution as a positive response criterion.

Annual review (4Q 2024) revised 'biomarkers' language to 'more broadly applicable assessments' and added MRE example to imaging-based assessment.

1FDA-approved indication(s)

F2-F3Covered fibrosis stages

12Approval duration (months)

Coverage Summary

Coverage: Covered with criteria for adults (≥18 years) with noncirrhotic metabolic dysfunction-associated steatohepatitis (MASH; formerly NASH) with stage F2–F3 fibrosis. Approval duration is 12 months. The FDA approval was granted under accelerated approval based on improvement in NASH and fibrosis, and continued approval may be contingent upon confirmatory trials. Per FDA-labeled limitations, avoid use in patients with decompensated cirrhosis.

Initial Therapy Criteria

Initial Approval Criteria

Rezdiffra is medically necessary when ALL of the following are met:

ALL of the following

Diagnosis of metabolic dysfunction-associated steatohepatitis (MASH; formerly known as NASH).
Prescribed by or in consultation with a hepatologist or gastroenterologist.
Document consultation when applicable.
ALL of the following
- fibrosis confirmation methods
  - Liver biopsy.
  - Serum-based assessment (e.g., fibrosis-4 [FIB-4], NAFLD fibrosis score [NFS], enhanced liver fibrosis [ELF]).
  - Imaging-based assessment (e.g., FibroScan, magnetic resonance elastography [MRE], magnetic resonance imaging proton density fat fraction [MRI-PDFF]).
  - MEFIB score (as measured by FIB-4 and MRE).
  - MAST score (as measured by MRI-PDFF, MRE, and serum AST).
Age 18 years or older.Age >= 18 years
If body mass index (BMI) >= 25 kg/m2, documentation of adherence to lifestyle modification, including participation in a physician-directed diet and exercise program, for at least the last 6 months.BMI >= 25 kg/m2
ALL of the following
- Actual body weight < 100 kg: 80 mg per day.Weight < 100 kg: 80 mg PO daily
- Actual body weight >= 100 kg: 100 mg per day.Weight >= 100 kg: 100 mg PO daily
Prescriber attestation that member is currently receiving standard of care management for concomitant related conditions (including type 2 diabetes, dyslipidemia, and hypertension).
See Appendix D for examples of standard of care

Operational note: Dosing is weight-based and limited to one tablet daily—80 mg for actual body weight <100 kg and 100 mg for actual body weight ≥100 kg per the prescribing information. This agent is FDA-approved under accelerated approval for adults with noncirrhotic NASH/MASH with F2–F3 fibrosis; continued approval may depend on confirmatory trials. Avoid use in patients with decompensated cirrhosis (limitation of use).

Continuation Therapy Criteria

Member must meet ONE of the following:

ANY of the following

Metabolic Dysfunction-Associated Steatohepatitis (must meet all):
- Member is currently receiving medication via Centene benefit or member has previously met initial approval criteria.
- Member is responding positively to therapy as evidenced by improvement in at least one of the following parameters:
- Response evidence (all of the following must be documented):
  - Improvement in fibrosis of >= 1-stage from baseline>= 1-stage

Diagnoses / Indications Not Authorized

Diagnoses/Indications Not Authorized

Coverage is NOT authorized for:

ANY of the following

Non-FDA approved indications that are not addressed in this policy, unless sufficient documentation exists per off-label use policies (CP.CPA.09 commercial, HIM.PA.154 marketplace, CP PMN.53 Medicaid).
See off-label policies listed
Use in patients with decompensated cirrhosis (limitation of use per FDA labeling).
Avoid use in decompensated cirrhosis

Off‑label requests: For non‑FDA approved indications or uses not addressed in this policy, providers may submit off‑label justification consistent with the referenced Centene off‑label use policies (CP.CPA.09, HIM.PA.154, CP PMN.53).

Applicable Codes & Related Policies

Policy identifiersmixed

CP PHAR.647

Clinical policy reference number

Related Centene policies referencedmixed

CP.CPA.190	No coverage criteria policy (commercial)
HIM.PA.33	No coverage criteria policy (marketplace)
CP PMN.255	No coverage criteria policy (Medicaid)
HIM.PA.103	Non-formulary policy (marketplace)
CP PMN.16	Non-formulary policy (Medicaid)
CP.CPA.09	Off-label use policy (commercial)
HIM.PA.154	Off-label use policy (marketplace)
CP PMN.53	Off-label use policy (Medicaid)

Evidence and policy details: Key evidence includes Harrison SA et al., Phase 3 trial of resmetirom in NASH with liver fibrosis (N Engl J Med 2024) and the Rezdiffra Prescribing Information (Madrigal Pharmaceuticals; March 2024). Policy number: CP PHAR.647. Effective date: 03.14.24. Last review: 11.24.

Provider Actions & Documentation Requirements

Documentation Required

Support documentation at time of request

Support documentation at time of request: submit office chart notes, relevant laboratory results, and imaging or biopsy reports that demonstrate MASH with stage F2–F3 fibrosis confirmed within the last 6 months. If BMI ≥ 25 kg/m2, include documentation of adherence to lifestyle modification (participation in a physician‑directed diet and exercise program) for at least the last 6 months.

Office chart notes
Laboratory results (e.g., FIB‑4, NFS, ELF)
Imaging or biopsy reports (e.g., FibroScan, MRE, MRI‑PDFF, liver biopsy)
Fibrosis confirmation dated within the last 6 months
Lifestyle modification documentation for BMI ≥ 25 kg/m2 (physician‑directed diet and exercise participation ≥ 6 months)

Clinical Evidence & Background

RezdiffraDrug (brand) - Resmetirom (Rezdiffra)

FDA-accelApproval: Accelerated approval for adults with noncirrhotic NASH/MASH (F2-F3)

Avoid:decompLimitation: Avoid use in decompensated cirrhosis (FDA-labeled)

DoseWeight-based dosing: <100 kg = 80 mg PO daily; >=100 kg = 100 mg PO daily; max 1 tablet/day

Background and glossary: Resmetirom (Rezdiffra) is a thyroid receptor beta agonist approved under accelerated approval for adults with noncirrhotic MASH (formerly NASH) with moderate to advanced fibrosis (F2–F3). Continued approval may be contingent on confirmatory trials. The FDA labeling includes a limitation to avoid use in decompensated cirrhosis. Definitions/clarifications: MASH = metabolic dysfunction‑associated steatohepatitis (formerly NASH); MA SLD = metabolic dysfunction‑associated steatotic liver disease (formerly NAFLD); FIB‑4 = fibrosis‑4 serum score; MRE = magnetic resonance elastography.

Revision History

2024-03-14revised

2024-07-15revised

Multiple revisions noted across RTI and P&T approval dates; references and examples (MRE) added and some redirections removed per competitive analysis. (References reviewed and Drug updated.)

2024-11-24revisedLatest