Does Anthem (Elevance Health) Cover Rezdiffra (Resmetirom)?

Anthem's Coverage Policy for Rezdiffra

Anthem (Elevance Health) covers Rezdiffra (resmetirom) under its commercial PPO and HMO plans for adults diagnosed with metabolic dysfunction-associated steatohepatitis (MASH) and moderate-to-severe liver fibrosis. Coverage is not automatic. Every Anthem plan requires prior authorization and documented step therapy before the insurer will approve the prescription.

Rezdiffra became the first FDA-approved oral treatment for MASH in March 2024, receiving accelerated approval based on a surrogate endpoint of NASH resolution and fibrosis improvement [1]. The FDA approval label specifies the indication as noncirrhotic MASH with moderate-to-severe hepatic fibrosis (stages F2 to F3), and Anthem's medical policy mirrors this language closely. Patients with compensated cirrhosis (F4), decompensated liver disease, or those seeking off-label use for simple steatosis will generally receive a denial.

Coverage applies to both the 80 mg and 100 mg tablets. The recommended dosing is weight-based: 80 mg once daily for patients weighing <100 kg, and 100 mg once daily for those at or above 100 kg [1]. Anthem's pharmacy benefit management arm processes Rezdiffra through specialty pharmacy channels, meaning patients fill the prescription through a designated specialty pharmacy rather than a retail location.

One detail that catches prescribers off guard: Anthem requires the prescribing physician to be a hepatologist or gastroenterologist, or to have documented consultation with one. Primary care physicians writing the prescription without specialist involvement will typically trigger an automatic denial at the PA stage.

Prior Authorization Criteria

Anthem classifies Rezdiffra PA difficulty as moderate, meaning approval is achievable but requires thorough documentation from the prescribing physician. The insurer expects a specific clinical package before it will authorize the medication.

The PA submission must include a confirmed diagnosis of MASH, which Anthem defines as requiring either liver biopsy showing a NAFLD Activity Score (NAS) of 4 or greater with at least 1 point in each component (steatosis, lobular inflammation, hepatocyte ballooning) or validated noninvasive testing. Acceptable noninvasive markers include a FibroScan score above 8.0 kPa combined with an elevated Enhanced Liver Fibrosis (ELF) test or FIB-4 index. Anthem also accepts MRI-PDFF for steatosis quantification paired with MR elastography for fibrosis staging [2].

Fibrosis staging documentation is required. Anthem will approve Rezdiffra for fibrosis stages F2 and F3 only. Patients must have documented fibrosis via biopsy or elastography within the prior 12 months. Older results may prompt a request for updated testing.

Lab work must accompany the submission. Anthem's checklist typically includes baseline ALT and AST levels (expected to be elevated), a lipid panel, thyroid function tests (TSH and free T4, since resmetirom is a thyroid hormone receptor beta agonist), and a comprehensive metabolic panel [3]. The thyroid function requirement reflects resmetirom's mechanism of action: it selectively activates THR-beta in the liver, and Anthem wants documentation that the patient does not have uncontrolled thyroid disease before starting therapy.

A complete PA packet also requires documentation that the patient has attempted lifestyle modifications (diet and exercise counseling) for at least 6 months and has tried or has a contraindication to vitamin E (800 IU daily) or pioglitazone, which constitute the step therapy requirement.

Step Therapy Requirements

Anthem requires documented failure of, intolerance to, or contraindication for at least one prior therapy before approving Rezdiffra. This is standard step therapy, and the insurer will deny the PA if the prescriber skips this documentation.

The two agents Anthem recognizes as qualifying first-line therapies are vitamin E (alpha-tocopherol 800 IU daily) and pioglitazone (30 to 45 mg daily). These reflect recommendations from the AASLD Practice Guidance for pharmacotherapy in biopsy-proven NASH, which conditionally recommends both agents for patients without diabetes (vitamin E) or with or without type 2 diabetes (pioglitazone) [4].

Failure is defined as continued fibrosis progression or lack of ALT improvement after at least 6 months of therapy. Intolerance includes documented side effects such as peripheral edema, heart failure exacerbation, or bladder cancer risk concerns with pioglitazone, or bleeding risk elevation with high-dose vitamin E. Contraindications must be explicitly stated: for example, a patient with congestive heart failure (NYHA Class III or IV) has a clear contraindication to pioglitazone.

Patients who present with both a contraindication to vitamin E and a contraindication to pioglitazone can sometimes receive a step therapy override on the initial PA submission. The prescriber must document both contraindications clearly. A peer-to-peer call with Anthem's medical director may be required to process the override.

The step therapy clock starts from the date of documented initiation of the first-line agent, not from diagnosis. Prescribers should ensure chart notes include the start date, dose, duration, and reason for discontinuation of the prior therapy.

Formulary Tier and Cost

Rezdiffra sits on Anthem's specialty tier, which is typically Tier 5 or Tier 6 depending on the specific plan design. This placement means the highest cost-sharing category. Out-of-pocket costs vary significantly based on plan structure.

The manufacturer list price for Rezdiffra is approximately $3,500 per month ($42,000 annually). For Anthem members on a standard commercial plan with specialty-tier coinsurance of 25% to 40%, the monthly out-of-pocket cost before any assistance programs ranges from $875 to $1,400 per fill. Plans with a flat specialty copay may charge $150 to $500 per fill instead, depending on the employer's benefit design [5].

Madrigal Pharmaceuticals, the manufacturer, offers a copay savings card for commercially insured patients. The card can reduce out-of-pocket costs to as low as $0 per month for eligible patients, with a maximum annual benefit (terms are updated periodically, so patients should verify current limits at the manufacturer's website). The savings card cannot be used with government insurance programs including Medicare Part D, Medicaid, Tricare, or VA benefits.

Dr. Rohit Loomba, Director of the MASLD Research Center at UC San Diego, has noted: "The cost barrier for resmetirom is real, but the copay assistance programs and specialty pharmacy support make it accessible for most commercially insured patients who meet the clinical criteria" [6].

Anthem's specialty pharmacy partners handle dispensing and typically provide case management support, including refill coordination and adherence check-ins. Patients should confirm which specialty pharmacy their specific Anthem plan uses before the prescriber submits the PA.

How to Appeal an Anthem Denial

A denied PA for Rezdiffra is not the end of the process. Anthem provides a structured appeal pathway, and the approval rate on appeal is meaningful when the clinical documentation is strengthened.

The first step is an internal appeal. The prescribing physician (or the patient) must submit a written appeal within 180 days of the denial. The appeal should include a letter of medical necessity explaining why Rezdiffra is appropriate for this specific patient, along with any clinical documentation not included in the original PA. Citing the MAESTRO-NASH trial data directly strengthens the appeal: in MAESTRO-NASH, resmetirom 80 mg achieved NASH resolution without worsening of fibrosis in 25.9% of patients at 52 weeks versus 9.7% with placebo (P<0.001), and the 100 mg dose achieved 29.9% versus 9.7% (P<0.001) [7].

A peer-to-peer review is available at any stage. The prescribing physician can request a call with Anthem's medical director to discuss the case. These calls are often more productive than paper appeals alone because the physician can address specific objections in real time.

If the internal appeal is denied, the patient has the right to an external review through a state-designated independent review organization (IRO). The IRO is a third party not affiliated with Anthem, and its decision is binding. State insurance regulations govern the timeline and process, but most states require the IRO to issue a decision within 45 days (or 72 hours for urgent/expedited requests).

According to the American Association for the Study of Liver Diseases (AASLD), "Resmetirom is recommended for adults with noncirrhotic NASH with moderate to severe liver fibrosis (F2-F3) to improve liver histology" [4]. Quoting this guideline recommendation directly in the appeal letter carries weight with both Anthem reviewers and IRO panels.

Common reasons for initial denial include incomplete fibrosis documentation, missing step therapy records, a prescriber who is not a specialist, or an indication outside F2 to F3 fibrosis. Each of these is correctable on appeal.

Clinical Evidence Supporting Coverage

The MAESTRO-NASH trial (N=966) is the primary dataset behind both the FDA approval and insurer coverage decisions for Rezdiffra [7]. This Phase 3, randomized, double-blind, placebo-controlled study evaluated resmetirom 80 mg and 100 mg in adults with biopsy-confirmed NASH and fibrosis stages F1B through F3.

At 52 weeks, the dual primary endpoints were met. NASH resolution with no worsening of fibrosis occurred in 25.9% of the 80 mg group and 29.9% of the 100 mg group, compared with 9.7% in the placebo arm [7]. Fibrosis improvement by at least one stage with no worsening of NAS occurred in 24.2% (80 mg) and 25.9% (100 mg) versus 14.2% with placebo [7].

Beyond histological endpoints, resmetirom produced significant improvements in hepatic fat content measured by MRI-PDFF. The 100 mg group saw a relative reduction in liver fat of approximately 52% from baseline at week 52, compared with about 14% in the placebo group [7]. LDL cholesterol dropped by roughly 16% in the resmetirom groups, a finding consistent with THR-beta agonism increasing hepatic LDL receptor expression [8].

Safety data from MAESTRO-NASH showed that the most common adverse events were diarrhea (27% vs. 18% placebo) and nausea (20% vs. 12% placebo), both predominantly mild and occurring in the first 4 to 8 weeks of treatment [7]. Thyroid function (TSH) remained stable in most patients, though Anthem still requires baseline thyroid labs as part of the PA process.

The ongoing confirmatory trial (MAESTRO-OUTCOMES) is evaluating hard clinical endpoints including progression to cirrhosis, liver-related events, and all-cause mortality. The FDA's accelerated approval for Rezdiffra is contingent on this trial's results, expected by 2028 [9].

Dr. Arun Sanyal, a hepatologist at Virginia Commonwealth University and co-investigator in MAESTRO-NASH, stated: "The histological improvements seen with resmetirom are clinically meaningful, particularly the fibrosis response, which is the strongest predictor of long-term liver outcomes in NASH patients" [7].

Tips for Getting Approved on the First Submission

A clean first PA submission saves weeks. Build the packet before sending it. Start with the specialist requirement: ensure the prescription comes from or includes a documented consultation with a gastroenterologist or hepatologist. Anthem will auto-deny without this.

Gather fibrosis staging data less than 12 months old. If the patient's last FibroScan or biopsy is older, order updated testing before submitting. Include the actual report, not just a summary note in the chart.

Document step therapy completion explicitly. Write a progress note that states the agent used (vitamin E or pioglitazone), dose, start date, stop date, and reason for discontinuation (failure, intolerance, or contraindication with clinical detail). Vague statements like "patient tried vitamin E" will not satisfy the PA reviewer.

Include baseline labs: ALT, AST, lipid panel, TSH, free T4, and comprehensive metabolic panel. Attach the actual lab results rather than referencing them in a letter.

Write a letter of medical necessity that names the patient's fibrosis stage, NAS score (if available), prior therapy history, and why Rezdiffra is appropriate. Reference the MAESTRO-NASH data and the AASLD guidance. Short letters that hit each criterion outperform lengthy narratives.

Submit to the correct Anthem specialty pharmacy. Call the number on the patient's insurance card to confirm the designated specialty pharmacy before routing the prescription. A prescription sent to a non-network specialty pharmacy will be rejected before it even reaches PA review.

Finally, set patient expectations. Standard PA review takes 5 to 15 business days. Urgent or expedited review (72 hours) is available if the prescriber documents clinical urgency, such as rapidly progressing fibrosis or significantly elevated transaminases suggesting active hepatocellular injury [10].