Rezdiffra (Resmetirom) HSA/FSA Eligibility and Submission: Complete 2026 Guide

What Is Rezdiffra and Why Does Cost Access Matter?

Rezdiffra (resmetirom) is the first drug approved by the FDA for metabolic dysfunction-associated steatohepatitis (MASH), previously called nonalcoholic steatohepatitis (NASH), with noncirrhotic liver fibrosis at stages F2 or F3. The FDA granted approval on March 14, 2024, based on the MAESTRO-NASH trial. [1]

MASH affects an estimated 1.5 to 6.5 percent of U.S. Adults, with a meaningful fraction progressing to cirrhosis or hepatocellular carcinoma if untreated. [2] Resmetirom works as a thyroid hormone receptor-beta (THR-beta) selective agonist, reducing hepatic lipid accumulation and fibrosis progression. [3]

The Cost Problem Is Real

The wholesale acquisition cost (WAC) for resmetirom sits at roughly $47,400 per year as of 2025. That figure does not reflect what most insured patients pay, but it sets the floor for list-price calculations that affect deductibles, prior authorization decisions, and out-of-pocket maximums. [4]

Because MASH is a chronic condition requiring long-term treatment, understanding every cost-offset tool, HSA, FSA, manufacturer copay assistance, and patient assistance programs, is not optional for most patients. It is the difference between filling the prescription and abandoning therapy.

The Regulatory Background

The FDA approved resmetirom under the accelerated approval pathway based on histological endpoints (NASH resolution and fibrosis improvement) from MAESTRO-NASH. [1] In that trial (N=966), 25.9% of patients on resmetirom 80 mg and 29.9% on 100 mg achieved NASH resolution with no worsening of fibrosis at week 52, versus 9.7% on placebo (P<0.001). [5] Fibrosis improvement of at least one stage was achieved by 24.2% (80 mg) and 25.9% (100 mg) versus 14.2% placebo (P<0.001). [5]

HSA Eligibility for Rezdiffra: The Short Answer

Rezdiffra qualifies as an HSA-eligible expense. Any prescription drug dispensed by a licensed pharmacist and prescribed by a physician for a diagnosed medical condition meets the IRS definition of a "qualified medical expense" under Section 213(d) of the Internal Revenue Code and IRS Publication 502. [6]

IRS Publication 502 and Prescription Drugs

IRS Publication 502 states that you can include in medical expenses amounts paid for prescribed medicines or drugs. A prescribed drug is one that requires a prescription by a licensed health professional. [6] Resmetirom unambiguously requires a prescription and is dispensed only for a specific IRS-recognized diagnosis (liver disease / hepatitis), so no additional documentation is needed to establish eligibility in principle.

The practical test your HSA administrator will apply:

1. Was the expense a prescription drug? (Yes.)
2. Was it prescribed by a licensed clinician? (Yes.)
3. Was it for a diagnosed medical condition, not cosmetic or general wellness? (Yes, fibrosis-stage MASH.)

What Documentation Your HSA Administrator Needs

Most HSA administrators follow the same documentation checklist. Gather these before submitting:

• Itemized pharmacy receipt showing drug name (resmetirom or Rezdiffra), National Drug Code (NDC), dispensing date, quantity, and total amount charged.
• Explanation of Benefits (EOB) from your health insurer showing what the plan paid and what you owe.
• Prescriber information (name, NPI, and practice address may be required on some forms).
• Your HSA claim form, download from your administrator's portal (Fidelity, HSA Bank, HealthEquity, etc.).

Submit within the deadline your plan specifies. Most HSA plans allow reimbursement claims for the same calendar year; some allow a grace period or rollover, but rules vary. [6]

HSA vs. FSA: Key Operational Differences

| Feature | HSA | FSA | |---|---|---| | Ownership | Yours permanently | Employer plan; may forfeit unused funds | | Rollover | Unlimited | Typically $640 cap (2024 IRS limit) or grace period | | Eligible high-deductible plan required | Yes (HDHP) | No | | Rezdiffra eligible | Yes | Yes | | Substantiation required | Yes | Yes |

Both account types use the same IRS Section 213(d) definition, so Rezdiffra is eligible for FSA reimbursement on identical grounds. [6]

FSA Eligibility for Rezdiffra: Step-by-Step Submission

Submitting a Rezdiffra charge to your FSA follows the same documentation path as HSA, with one additional consideration: FSA funds are plan-year funds, meaning the expense date matters more than the payment date in some plans.

Step 1: Fill Your Prescription

Use a pharmacy in your insurance network where possible. Ask the pharmacist to print an itemized receipt (not just a cash-register receipt) that shows:

• Drug name and strength (resmetirom 80 mg or 100 mg tablet)
• NDC number
• Days supply and quantity
• Prescribing provider

Step 2: Obtain Your EOB

Log into your insurance portal 7 to 14 days after the prescription is filled. Download or print the EOB for that claim. The EOB is often required to prove the insurer processed the claim before FSA reimbursement, preventing double-dipping.

Step 3: Complete the FSA Claim Form

Download the claim form from your FSA administrator. Common administrators include WageWorks/HealthEquity, Optum Financial, Benefit Resource Inc. (BRI), and TASC. Each form asks for:

• Patient name and date of birth
• Service date (date prescription was filled)
• Provider name (pharmacy or prescribing physician)
• Expense type (prescription drug)
• Amount claimed

Step 4: Submit and Track

Most administrators accept electronic submission through a mobile app or web portal. Paper forms can be faxed or mailed. Processing typically takes 5 to 10 business days. Keep copies of everything.

Rezdiffra Cost Assistance Beyond HSA/FSA

HSA and FSA reimbursement offset your out-of-pocket share, but they do not reduce the underlying price. Several programs attack the cost from the other direction.

Madrigal RESOLVE Patient Support Program

Madrigal Pharmaceuticals operates the RESOLVE support program for commercially insured patients. Eligible patients may pay as little as $0 per month through the copay assistance component. Income limits and insurance type restrictions apply, patients with government insurance (Medicare, Medicaid, VA, TRICARE) are generally excluded from manufacturer copay programs per federal anti-kickback guidelines. [7]

To enroll, contact Madrigal's support line or visit the Rezdiffra manufacturer website. A patient navigator will walk through eligibility verification, prior authorization support, and specialty pharmacy coordination.

Prior Authorization: What to Expect

Most commercial insurance plans require prior authorization (PA) for Rezdiffra. The PA criteria typically align with the FDA-approved label: [1]

• Confirmed MASH diagnosis (liver biopsy or validated non-invasive test showing F2-F3 fibrosis)
• BMI and metabolic risk factor documentation
• Evidence that lifestyle modification has been attempted

Physicians should document fibrosis staging with FibroScan (liver stiffness measurement), MRI-PDFF, or liver biopsy. The AASLD and EASL 2023 guidance on MASH management supports non-invasive testing as an acceptable alternative to biopsy for staging in appropriate clinical contexts. [8]

Specialty Pharmacy Dispensing

Rezdiffra is distributed through specialty pharmacies. Specialty pharmacies often have their own financial counselors who can identify additional assistance programs, manufacturer vouchers, and foundation grants simultaneously. Ask the specialty pharmacy to run a full benefits investigation before the first fill.

Patient Assistance Programs (PAPs)

Patients who are uninsured or underinsured and do not qualify for the commercial copay program may apply to Madrigal's Patient Assistance Program for free or reduced-cost medication. Eligibility is typically income-based (often at or below 400-600% of the federal poverty level) and requires annual recertification.

Independent Charitable Foundations

Disease-specific foundations sometimes provide medication grants. HealthWell Foundation and Patient Advocate Foundation operate co-pay relief funds that may cover Rezdiffra for eligible patients. Fund availability changes monthly; apply early in the calendar year when funds are most likely open.

Insurance Coverage Field for Rezdiffra in 2026

Coverage has expanded since the March 2024 approval, but it remains inconsistent across payers.

Commercial Insurance

Major commercial carriers (UnitedHealthcare, Aetna, Cigna, Blue Cross Blue Shield plans) have issued coverage policies for resmetirom, typically requiring PA and documentation of F2-F3 fibrosis. Step-therapy requirements mandating prior failure of lifestyle intervention or a specific duration of optimized metabolic management are common. [9]

Medicare and Medicaid

Medicare Part D plans are required to cover FDA-approved drugs for approved indications, but formulary tier placement varies. Resmetirom landed on specialty tiers (Tier 4-5) at most Part D plans as of 2025, which means significant cost-sharing before out-of-pocket maximums kick in.

Medicare patients cannot use manufacturer copay assistance. The Medicare Extra Help (Low Income Subsidy) program may reduce Part D cost-sharing for qualifying patients. [10]

Medicaid coverage is state-specific. As of early 2026, coverage decisions vary widely. Check your state Medicaid formulary directly.

Appeals and Step Therapy Overrides

If a prior authorization is denied:

1. Request a peer-to-peer review between your physician and the insurance medical director.
2. Submit a formal appeal with supporting clinical documentation (biopsy report, FibroScan results, labs).
3. If the condition worsens while waiting, document clinical urgency to support an expedited appeal.

The Consolidated Appropriations Act and various state step-therapy override laws require insurers to grant exceptions when step therapy is contraindicated or the patient has previously failed the required drug. [11]

Clinical Context: Why Treating MASH Matters for Coverage Arguments

Understanding the clinical stakes strengthens prior authorization letters and insurance appeals. Untreated MASH with fibrosis carries a meaningful risk of progression. A meta-analysis of paired liver biopsies found that fibrosis progresses by at least one stage in approximately 40% of MASH patients over a median follow-up of 5.9 years. [12]

MAESTRO-NASH Trial Results in Detail

The MAESTRO-NASH trial (ClinicalTrials.gov NCT03900429, N=966) was a randomized, double-blind, placebo-controlled Phase 3 study. [5] Patients received resmetirom 80 mg, resmetirom 100 mg, or placebo once daily for 52 weeks.

Co-primary endpoints were NASH resolution without worsening of fibrosis and fibrosis improvement of at least one stage without worsening of NASH. Both doses met both endpoints at P<0.001 versus placebo. [5]

Secondary lipid endpoints also showed improvement. LDL cholesterol decreased by 13.6% (80 mg) and 16.3% (100 mg) from baseline versus a 0.1% decrease with placebo. [5] These lipid benefits may support additional coverage arguments for patients with concurrent dyslipidemia. [13]

Dose Selection and Titration

The FDA-approved starting dose is 80 mg once daily. After four weeks, the dose may be increased to 100 mg once daily based on tolerability. Hepatic impairment affects drug exposure: resmetirom is contraindicated in cirrhosis (Child-Pugh B or C) given CYP2C8 metabolism and transporter interactions. [1]

Drug interactions are clinically relevant. Resmetirom is a substrate of CYP2C8 and OATP1B1/1B3 transporters. Strong CYP2C8 inhibitors (e.g., gemfibrozil) increase resmetirom exposure significantly. [1] Co-administration with statins requires monitoring given shared transporter pathways. [14]

Documenting Medical Necessity for Insurance and HSA/FSA Purposes

Both payers and HSA/FSA administrators may request documentation of medical necessity for specialty drugs. A strong medical necessity letter from the prescribing hepatologist or gastroenterologist should include:

• ICD-10 code: K75.81 (Nonalcoholic steatohepatitis, NASH), the current coding term for MASH in ICD-10-CM as of 2025.
• Fibrosis staging results (FibroScan kPa value, MRI-PDFF percentage, or biopsy pathology report with NASH Activity Score).
• Prior treatment history and lifestyle intervention documentation.
• Statement of clinical urgency referencing fibrosis progression risk.
• Reference to the FDA-approved indication for resmetirom per the prescribing information. [1]

The American Association for the Study of Liver Diseases (AASLD) 2023 practice guidance on MASH provides a peer-reviewed framework that physicians can cite directly in PA letters. [8] The European Association for the Study of the Liver (EASL) published updated clinical practice guidelines on MASH in 2024, which insurers operating internationally may also recognize. [15]

FibroScan Threshold Reference Points

| Liver Stiffness (kPa) | Approximate Fibrosis Stage | |---|---| | <7.0 | F0-F1 (minimal fibrosis) | | 7.0-9.5 | F2 (moderate fibrosis) | | 9.5-12.5 | F3 (advanced fibrosis) | | >12.5 | F4 / cirrhosis |

These are approximate thresholds; the specific validated cutoffs depend on the etiology and FibroScan probe used. [16] Payer PA criteria often specify the F2-F3 range to align with the FDA-approved indication.

Practical Checklist: HSA/FSA Submission for Rezdiffra

Use this checklist for every fill:

• [ ] Confirm prescription is filled at an in-network specialty pharmacy.
• [ ] Request itemized receipt with drug name, NDC, date, quantity, and total cost.
• [ ] Download EOB from insurance portal (wait 7-14 days post-fill).
• [ ] Verify expense date falls within your HSA/FSA plan year.
• [ ] Complete plan administrator's claim form (electronic preferred).
• [ ] Attach itemized receipt and EOB as PDF or high-resolution image.
• [ ] Submit before your plan's deadline (typically 90 days post-expense for FSA).
• [ ] Save confirmation number and resubmit documentation if denied.

Frequently Asked Questions