ModifiedCignaPolicy IP0642

Rezdiffra

Defines prior authorization, eligibility, and continuation criteria for Rezdiffra (resmetirom) for adults with non-cirrhotic NASH/MASH with moderate to advanced (F2–F3) fibrosis for Cigna-administered health benefit plans.

Policy Summary

PayerCigna

PolicyRezdiffra

Policy CodePolicy IP0642

Change TypeMaterial revisions to initial and continuation documentation and time windows

Effective DateAug 15, 2025

Next Review Date

Key ActionSubmit prior authorization documentation demonstrating qualifying biopsy within 3 years or imaging within 6 months, fibrosis stage F2–F3, metabolic risk factors, alcohol use limits, and prescriber specialty to obtain approval for 1 year.

SourceLink

POLICY UPDATE CHANGES

For patients currently receiving Rezdiffra, the requirement that the patient completed ≥1 and <2 years with evidence of benefit was removed; now a patient who has completed ≥1 year may be approved if they have not had worsening of fibrosis or MASH/NASH per prescriber.

Timeframe for liver biopsy documentation for initial therapy changed from within 6 months to within 3 years preceding treatment with Rezdiffra.

The histologic requirement for NAFLD activity score was modified so component scores require ≥1 (instead of >1) for steatosis, ballooning, and lobular inflammation.

The allowable timeframe for an imaging exam in initial therapy documentation was changed from within 3 months to within 6 months preceding treatment.

The policy clarifies that Rezdiffra is indicated for non‑cirrhotic NASH; safety/effectiveness in NASH cirrhosis has not been established.

F2–F3target fibrosis stages for coverage

≥18

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Coverage Criteria for Rezdiffra (resmetirom)

Initial Therapy — Approve for 1 year if the patient meets ALL of the following (A.i–vii):

Approve for 1 year if the patient meets ALL of the following (A.i–vii):

Initial Therapy criteria

Diagnostic confirmation of MASH/NASH: Prior to treatment, diagnosis of MASH/NASH is confirmed by ONE of the following: (a) liver biopsy performed within the 3 years preceding treatment that shows NAFLD activity score ≥ 4 with component scores ≥ 1 for steatosis, ballooning, and lobular inflammation; OR (b) imaging exam (elastography, CT, or MRI) performed within 6 months preceding treatment demonstrating disease consistent with NASH;biopsy within 3 years OR imaging within 6 months; component scores ≥1
Documentation required for biopsy or imaging as specified.
Fibrosis stage: Patient has stage F2 fibrosis OR stage F3 fibrosis (documentation required).F2 or F3
Metabolic risk factors: According to the prescriber, patient has three or more metabolic risk factors managed per standard of care: central obesity; hypertriglyceridemia; reduced HDL cholesterol; hypertension; elevated fasting plasma glucose (diabetes or pre-diabetes).≥ 3 metabolic risk factors
Documentation of risk factors required.
Alcohol use limits: According to the prescriber, patient meets ONE of: female patient alcohol consumption < 20 grams/day; OR male patient alcohol consumption < 30 grams/day.Female < 20 g/day; Male < 30 g/day
Concurrent management and prescriber: Medication will be used in combination with appropriate diet and exercise therapy; AND medication is prescribed by or in consultation with an endocrinologist, gastroenterologist, or hepatologist.
Prescriber specialty and combination therapy must be documented.

Initial Therapy — Covered when ALL of the following are met for initial therapy in non‑cirrhotic NASH:

Covered when ALL of the following are met for initial therapy in non‑cirrhotic NASH:

Histology or imaging documentation: Documentation via liver biopsy within 3 years preceding treatment OR imaging exam within 6 months preceding treatment demonstrating disease consistent with NASH; when biopsy is used, histology must show NAFLD activity score components with scores ≥1 in steatosis, ballooning, and lobular inflammation.biopsy within 3 years OR imaging within 6 months; component scores ≥1

Documentation required; timeframe updated per revision details.

Non‑cirrhosis requirement: Patient must not have cirrhosis; Rezdiffra is indicated for non‑cirrhotic NASH with moderate to advanced fibrosis. Safety and effectiveness in NASH cirrhosis have not been established.no cirrhosis

MAESTRO‑NASHOUTCOMES trial assessing compensated cirrhosis ongoing.

Continuation / Currently Receiving Rezdiffra — Approve for 1 year if the patient meets ALL of the following (B.i–vi):

Approve for 1 year if the patient meets ALL of the following (B.i–vi):

Continuation Therapy criteria: Patient has completed ≥ 1 year of therapy with Rezdiffra AND according to the prescriber has not had worsening of fibrosis or MASH/NASH; AND the patient has not progressed to stage F4 (cirrhosis); AND metabolic risk factors are managed according to standard of care; AND patient meets ONE of the following alcohol criteria: female < 20 g/day OR male < 30 g/day; AND medication is used in combination with appropriate diet and exercise therapy; AND medication is prescribed by or in consultation with an endocrinologist, gastroenterologist, or hepatologist.Completed ≥1 year of therapy; no progression to F4; Female <20 g/day OR Male <30 g/day

Patients with <1 year of therapy or restarting should be considered under Initial Therapy criteria; prescriber attestations required for fibrosis/NASH status and metabolic risk management.

Not Medically Necessary / Other Uses — Not medically necessary statements and exclusions

Not medically necessary uses: Use of Rezdiffra for indications other than non‑cirrhotic NASH/MASH with moderate to advanced fibrosis (F2–F3) is considered not medically necessary.

Includes use in NASH cirrhosis; safety and effectiveness in cirrhosis not established.

Continuation Therapy — Covered when ALL of the following are met for a patient currently receiving Rezdiffra:

Covered when ALL of the following are met for a patient currently receiving Rezdiffra:

Continuation criteria for patients on Rezdiffra: 1) Patient has completed ≥ 1 year of therapy with Rezdiffra AND according to the prescriber has not had worsening of fibrosis or MASH/NASH; 2) According to the prescriber, patient has not progressed to stage F4 (cirrhosis); 3) According to the prescriber, metabolic risk factors are managed according to standard of care; 4) According to the prescriber, patient meets ONE of: (a) Female patient: alcohol < 20 g/day; OR (b) Male patient: alcohol < 30 g/day; 5) Medication used in combination with appropriate diet and exercise therapy; 6) Medication prescribed by or in consultation with an endocrinologist, gastroenterologist, or hepatologist.Completed ≥1 year; Female <20 g/day OR Male <30 g/day; no progression to F4

Prescriber attestations are required for multiple elements including fibrosis/MASH status and metabolic risk management.

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Avoid use of Rezdiffra in patients with decompensated cirrhosis. The policy notes that Rezdiffra is indicated for non‑cirrhotic NASH with F2–F3 fibrosis and that safety and effectiveness have not been established in patients with NASH cirrhosis (including decompensated disease).

Rezdiffra for any use outside the approved indication for non‑cirrhotic NASH with F2–F3 fibrosis is considered not medically necessary. The policy explicitly states that the safety and effectiveness of Rezdiffra in NASH cirrhosis have not been established and that use for other indications is not covered.

Any use of Rezdiffra outside the FDA‑approved indication for non‑cirrhotic NASH (MASH) with moderate to advanced fibrosis (F2–F3) is considered not medically necessary. The policy clarifies that this includes treatment of NASH with cirrhosis because safety and effectiveness in NASH cirrhosis have not been established.

Use of Rezdiffra for indications other than non‑cirrhotic NASH (MASH) with moderate to advanced fibrosis (F2–F3) is considered not covered / not medically necessary. The policy specifically highlights that Rezdiffra is approved for non‑cirrhotic NASH and that the safety and effectiveness in NASH cirrhosis are not established, with ongoing trials (MAESTRO‑NASHOUTCOMES) evaluating use in compensated cirrhosis.

Coding and Diagnostic Guidance

Covered Codes (diagnosis/procedure guidance referenced)mixed

No codes listed

VCTE / LSM thresholds

LSM ≥ 8.0 kPaConsistent with clinically significant fibrosis (≥ F2)

LSM 8–12 kPaConsidered indeterminate risk; referral for hepatology, biopsy, MRE, or re-evaluation in 2–3 years recommended

LSM > 12 kPaIndicates high risk for advanced fibrosis (refer to hepatology)

Alcohol consumption limits

Female alcohol limit< 20 grams per day

Male alcohol limit< 30 grams per day

Definition context

Provider Actions, Prior Authorization, and Documentation

Prior Authorization

Prior Authorization Required for Rezdiffra

Prior authorization is required for prescription benefit coverage of Rezdiffra. All approvals are issued for 1 year when initial or continuation criteria are met. Rezdiffra must be prescribed by or in consultation with a specialist (endocrinologist, gastroenterologist, or hepatologist) given the specialized evaluation and monitoring required.

Prior authorization required for Rezdiffra; approvals valid for 1 year when criteria are met
Medication must be prescribed by or in consultation with an endocrinologist, gastroenterologist, or hepatologist

Prior Authorization

Prior Authorization Requirement

Prior authorization requires submission of the documentation items listed in the clinical criteria for either initial or continuation therapy. Documentation may include chart notes, laboratory results, medical test results, claims records, prescription receipts, and other relevant information.

Submit documentation specified in the applicable Initial Therapy or Continuation Therapy criteria

Background and Clinical Context

Metabolic dysfunction‑associated steatohepatitis (MASH), previously described as NASH, is a progressive liver disease associated with cardiometabolic risk factors. As fibrosis advances to stages F2–F3, the risk of adverse clinical outcomes increases. Rezdiffra is approved in adults for non‑cirrhotic NASH with moderate to advanced fibrosis (F2–F3) in combination with diet and exercise; ongoing trials are evaluating safety and efficacy in cirrhosis.

Definitions

MASH/NASH definition

TermMetabolic dysfunction-associated steatohepatitis (MASH)

Former namePreviously referred to as non-alcoholic steatohepatitis (NASH)

CharacterizationSubtype of MASLD; progressive form with hepatic steatosis plus hepatocellular damage and inflammation

NASH / MASH

Core featuresSteatosis plus inflammation and liver cell injury (distinguishes NASH/MASH from NAFLD)

Relation to NAFLDNAFLD includes steatosis; NASH/MASH additionally requires inflammation and hepatocellular injury

Implication for coverage

Policy Summary

PayerCigna

PolicyRezdiffra

Policy CodePolicy IP0642

Change TypeMaterial revisions to initial and continuation documentation and time windows

Effective DateAug 15, 2025

Next Review Date

SourceLink

On This Page

Denial Risk

Triggers for Denial

Progression to stage F4 (cirrhosis), excessive alcohol use above the sex-specific thresholds, lack of documentation that the patient has completed ≥ 1 year of therapy for continuation requests, and other unmet clinical criteria are triggers for denial of coverage.

Progression to stage F4 (cirrhosis) is a denial trigger for continuation
Alcohol consumption ≥ 20 g/day for females or ≥ 30 g/day for males may trigger denial
Continuation requests must document completion of ≥ 1 year of Rezdiffra therapy and no worsening of fibrosis or MASH/NASH

Documentation Required

Provider Documentation Types

Documentation is required for initial and continuation use of Rezdiffra and may include chart notes, laboratory results, imaging or biopsy reports, and other records as specified in the criteria.

Initial therapy: biopsy or imaging reports, fibrosis staging, metabolic risk factor documentation, alcohol use documentation, specialist involvement
Continuation therapy: documentation patient completed ≥ 1 year of therapy, no worsening of fibrosis/MASH/NASH, no progression to F4, alcohol use within thresholds, metabolic risk factors managed per standard of care