How to Get Rezdiffra (Resmetirom) in South Carolina

What Is Resmetirom and Why Was It Approved?

Resmetirom is a once-daily oral thyroid hormone receptor beta (THR-beta) selective agonist developed by Madrigal Pharmaceuticals. It is sold under the brand name Rezdiffra. The FDA granted accelerated approval on March 14, 2024, making it the first pharmacologic treatment approved specifically for MASH (previously called NASH) with moderate-to-advanced liver fibrosis. [1]

The Mechanism Behind THR-Beta Selectivity

THR-beta receptors concentrate in hepatocytes. Activating them increases fatty acid oxidation, reduces hepatic lipogenesis, and lowers LDL cholesterol without the cardiac side effects tied to systemic thyroid hormone excess. [2] This selectivity is why resmetirom can reduce liver fat and fibrosis without causing tachycardia or bone loss at therapeutic doses.

MAESTRO-NASH Trial Results

The key MAESTRO-NASH trial (N=966 patients, 52-week biopsy endpoint) published in the New England Journal of Medicine in 2024 showed that resmetirom 100 mg achieved NASH resolution without worsening fibrosis in 25.9% of patients versus 14.2% on placebo (P<0.001). [3] Fibrosis improvement by at least one stage occurred in 24.2% of the resmetirom 100 mg group compared with 14.6% on placebo (P<0.001). [3] The 80 mg dose also outperformed placebo on both co-primary endpoints, though the effect size was modestly smaller.

LDL-C decreased by a mean of 13.6% from baseline in the 100 mg group, a secondary finding with potential cardiovascular relevance given that MASH and atherosclerosis share metabolic drivers. [3]

FDA Label Restrictions

The FDA approval label restricts Rezdiffra to adults with non-cirrhotic MASH and fibrosis stage F2 or F3 confirmed by liver biopsy or by non-invasive tests (FibroScan, FIB-4, ELF score) consistent with at least moderate fibrosis. [1] Patients with Child-Pugh B or C cirrhosis, decompensated liver disease, or active alcohol-related liver disease are excluded from the approved indication. [1]

Who Qualifies for Rezdiffra in South Carolina?

Eligibility mirrors the FDA label. Qualifying patients must have biopsy-confirmed or non-invasively staged MASH with F2 or F3 fibrosis, no cirrhosis, and no active harmful alcohol use. Most insurers also require a BMI <27 exclusion check, a confirmed metabolic risk factor (type 2 diabetes, obesity, dyslipidemia, or hypertension), and documentation that lifestyle intervention has been attempted. [4]

Liver Fibrosis Staging Requirements

SC clinicians may use any of the following validated staging tools to document eligibility:

• Liver biopsy with NASH CRN scoring (gold standard)
• FibroScan (transient elastography) with liver stiffness measurement 8.2 to 12.5 kPa (suggesting F2, F3)
• FIB-4 index calculated from age, AST, ALT, and platelet count; a score above 1.30 warrants additional staging [5]
• Enhanced Liver Fibrosis (ELF) test score 9.8 or above, which correlates with at least F2 fibrosis [6]

The American Association for the Study of Liver Diseases (AASLD) 2023 Practice Guidance recommends non-invasive tests as acceptable first-line staging in patients with metabolic risk factors before liver biopsy is pursued. [4]

Metabolic Eligibility and Exclusions

Patients should have at least one of: BMI above 27, type 2 diabetes, hypertension, or atherogenic dyslipidemia. Exclusions include decompensated cirrhosis, active hepatitis B or C, drug-induced liver disease, autoimmune hepatitis, pregnancy, and current use of other thyromimetics. [1] Pregnancy is a hard contraindication because THR-beta agonism may disrupt fetal thyroid signaling. [2]

Required Labs and Workup Before Starting Rezdiffra in SC

Every SC prescriber, whether in a Greenville hepatology clinic or via telehealth, must document a baseline metabolic and liver panel before the first prescription. Prior authorization reviewers at commercial plans will reject claims lacking this documentation. [7]

Baseline Laboratory Panel

The following labs are standard before initiation:

• Comprehensive metabolic panel (CMP): ALT, AST, bilirubin, albumin, creatinine
• CBC with differential
• Fasting lipid panel: LDL-C, HDL-C, triglycerides, total cholesterol
• HbA1c (or fasting glucose if HbA1c is unavailable)
• TSH and free T4 (thyroid function affects THR-beta drug response) [2]
• Hepatitis B surface antigen and hepatitis C antibody to exclude viral hepatitis
• FIB-4 score calculation or FibroScan result documenting fibrosis stage [5]
• Pregnancy test in women of childbearing potential [1]

Monitoring Labs at Follow-Up

The FDA label recommends liver enzyme monitoring at 4 weeks, 12 weeks, and every 3 months thereafter. [1] ALT elevations above 3x the upper limit of normal occurred in approximately 3% of MAESTRO-NASH participants on the 100 mg dose, so baseline values are needed for comparison. [3] TSH should be rechecked at 12 weeks because resmetirom may suppress TSH in some patients, consistent with its mechanism. [2]

How to Get a Rezdiffra Prescription in South Carolina

South Carolina patients have three access pathways: in-person specialist referral, telehealth consultation with a SC-licensed provider, or a primary care physician with hepatology experience. Telehealth prescribing of controlled and non-controlled prescription drugs is explicitly permitted under SC Code of Regulations and the South Carolina Board of Medical Examiners policy as of 2024. [8]

Step-by-Step for In-Person Prescribing

1. Request a referral from your primary care physician to a hepatologist or gastroenterologist in SC (major centers include MUSC Health in Charleston, Prisma Health in Greenville and Columbia, and Lexington Medical Center).
2. Bring all prior imaging, FibroScan reports, or biopsy results to the consultation.
3. Complete baseline labs listed above if not already done.
4. The specialist submits a prior authorization to your commercial insurer using ICD-10 code K75.81 (MASH) and documentation of F2, F3 fibrosis.
5. If approved, the prescription is sent to a specialty pharmacy.
6. If denied, request a peer-to-peer review or file an appeal with supporting MAESTRO-NASH data. [3]

Telehealth Access in South Carolina

SC-licensed telehealth providers may prescribe Rezdiffra to SC residents without a prior in-person visit, provided the prescriber conducts a synchronous audio-visual consultation, reviews all labs and imaging, and documents a valid prescriber-patient relationship per SC Board of Medical Examiners guidelines. [8] HealthRX clinicians licensed in South Carolina follow this exact protocol.

The telehealth pathway is particularly useful for patients in rural SC counties (Georgetown, Marion, Allendale) where hepatology specialist wait times may exceed 90 days. A telehealth prescriber can initiate the prior authorization while the patient waits for a specialist appointment, avoiding a gap in care.

After the synchronous visit, the prescriber transmits the Rezdiffra prescription electronically to a specialty pharmacy. Most specialty pharmacies serving SC can fill and ship the prescription to the patient's home within 3 to 7 business days after insurance approval. [9]

Primary Care Physicians as Prescribers

South Carolina does not restrict Rezdiffra prescribing to specialists only. Any MD, DO, NP (with full practice authority or collaborative agreement), or PA (with a signed delegation agreement) licensed in SC may prescribe it, provided the clinical documentation supports the FDA indication. [8] PCPs with access to FibroScan or established FIB-4 workflows are increasingly managing MASH in primary care settings, consistent with the 2023 AASLD Practice Guidance encouraging a multidisciplinary approach. [4]

Prior Authorization in South Carolina: What Documents You Need

Prior authorization is required by nearly all SC commercial plans and both major SC Medicaid MCOs (though SC Medicaid does not cover Rezdiffra as of July 2025). The PA packet typically includes: [7]

• Clinical notes documenting MASH diagnosis with ICD-10 K75.81
• Fibrosis staging results (biopsy pathology report or FibroScan printout with kPa value and controlled attenuation parameter)
• Baseline labs (LFTs, lipid panel, TSH, HbA1c)
• Documentation of prior lifestyle intervention (dietitian notes, weight loss program records, or physician attestation)
• Letter of medical necessity citing MAESTRO-NASH trial data and the FDA-approved indication [3]
• Prescriber NPI and SC DEA/license number

What Happens If Prior Authorization Is Denied?

First-line denial is common for new drugs. The prescriber should request a peer-to-peer call within 72 hours. Madrigal Pharmaceuticals operates a patient support program called MadrigalONE that provides appeal letter templates, reimbursement support, and a patient assistance program for uninsured or underinsured SC patients. [9] The MadrigalONE hub can be reached at 1-833-696-2663.

If commercial insurance denies coverage after appeal, the patient assistance program may provide Rezdiffra at no cost for patients meeting income eligibility criteria (typically below 400% of the federal poverty level). [9]

SC Pharmacy Access: Specialty and 503A Options

Rezdiffra is distributed exclusively through specialty pharmacies enrolled in Madrigal's REMS-adjacent distribution network. SC-licensed specialty pharmacies, including Walgreens Specialty, CVS Specialty, and regional options like RxElite in Columbia, can dispense Rezdiffra to SC patients after a valid prescription and insurance approval are on file. [9]

503A Compounding Pharmacies in South Carolina

SC-licensed 503A compounding pharmacies may prepare compounded resmetirom for patients with a valid patient-specific prescription. Under federal law (21 U.S.C. 353a), 503A compounders may compound a drug that is commercially available if the prescriber documents a specific medical need for a different strength, dosage form, or excipient profile. [10] Because Rezdiffra is only available as 80 mg and 100 mg tablets, patients requiring intermediate dose titration or who cannot swallow tablets may have a documented medical need for a 503A compounded formulation.

SC-licensed 503A pharmacies must comply with both FDA guidance and SC Board of Pharmacy regulations. Patients should verify the pharmacy holds an active SC pharmacy permit before transferring a prescription. [10]

Prescription Transfers to South Carolina

Patients relocating to SC from another state can transfer an existing Rezdiffra prescription. SC law allows prescription transfer for non-controlled substances between licensed pharmacies. The receiving SC pharmacy will request the original prescription record from the out-of-state pharmacy. The prescriber does not need to rewrite the prescription unless it has expired, but a South Carolina-licensed provider must be on file for ongoing refills if the original prescriber is not licensed in SC. [8]

Rezdiffra Dosing, Side Effects, and Safety Monitoring in SC Clinical Practice

Dosing Protocol

The approved doses are 80 mg once daily for patients with moderate hepatic impairment and 100 mg once daily for most adults with adequate hepatic function. [1] The tablet is taken orally with or without food. No dose adjustment is required for renal impairment. Resmetirom is a CYP2C8 substrate; concurrent use with strong CYP2C8 inhibitors (gemfibrozil) may increase resmetirom exposure significantly and should be avoided. [1]

Common and Serious Adverse Effects

In MAESTRO-NASH, the most common adverse effects with resmetirom 100 mg were nausea (26% vs. 16% placebo) and diarrhea (28% vs. 17% placebo), both predominantly mild-to-moderate and occurring in the first 4 to 8 weeks. [3] Serious hepatic events were rare; ALT above 3x ULN occurred in 3.0% on 100 mg versus 1.4% on placebo. [3]

Gallstones and cholelithiasis require attention. Resmetirom increases bile cholesterol saturation via hepatic lipid flux changes; MAESTRO-NASH participants on 100 mg had a cholelithiasis rate of 5.7% compared with 3.0% on placebo. [3] SC clinicians should discuss this risk and consider baseline gallbladder ultrasound in patients with prior biliary symptoms. [4]

Drug Interactions Relevant to SC Patient Populations

South Carolina has relatively high rates of type 2 diabetes and statin use. [11] Resmetirom reduced LDL-C by 13.6% in MAESTRO-NASH, so statin doses may need downward adjustment at the 12-week follow-up visit to avoid excessive LDL-C lowering. [3] Resmetirom also inhibits OATP1B1 and OATP1B3 transporters, which can increase plasma concentrations of co-administered statins including rosuvastatin. [1] The FDA label recommends limiting rosuvastatin to 20 mg daily when co-prescribed with resmetirom. [1]

South Carolina Medicaid and Insurance Coverage

SC Medicaid (Healthy Connections) does not cover Rezdiffra as of July 2025. The South Carolina Department of Health and Human Services had not finalized a coverage policy for resmetirom at the time of publication. Patients on Medicaid should contact MadrigalONE (1-833-696-2663) immediately to assess patient assistance eligibility. [9]

Commercial Insurance in SC

The three largest SC commercial carriers (BlueCross BlueShield of SC, State Health Plan, Aetna SC) all require prior authorization but have active coverage policies for Rezdiffra when documentation meets their criteria. Typical PA criteria across these plans include:

• Confirmed MASH diagnosis with F2 or F3 fibrosis staging
• BMI above 27 or confirmed type 2 diabetes
• Documentation of lifestyle intervention for at least 6 months
• Prescriber attestation that the patient is not cirrhotic [7]

The South Carolina State Health Plan (covering state employees) has included Rezdiffra on its specialty tier formulary with a co-pay assistance cap of $150 per 30-day supply when combined with Madrigal's co-pay card. [9]

MASH Prevalence in South Carolina and Why Access Matters

MASH affects an estimated 1.5 to 6.5% of the U.S. Adult population, with prevalence higher in populations with obesity and type 2 diabetes. [12] South Carolina has one of the highest age-adjusted obesity rates in the Southeast at 36.3% of adults, according to CDC BRFSS 2023 data. [11] The state also reports a type 2 diabetes prevalence of 12.8%, above the national average of 11.6%. [11]

These figures suggest that a substantial proportion of SC adults may harbor occult MASH with fibrosis, most of whom have never been screened. The 2023 AASLD Practice Guidance states: "All patients with metabolic syndrome risk factors should be evaluated for MASLD/MASH, with non-invasive fibrosis staging offered to those with elevated liver enzymes or hepatic steatosis on imaging." [4] Rezdiffra's approval creates a clinical imperative to identify and treat these patients before progression to cirrhosis occurs, which carries a 5-year mortality exceeding 50% in decompensated cases. [12]

Comparing Access Pathways: Telehealth vs. In-Person in SC

| Access Route | Typical Wait Time | PA Submission | Best For | |---|---|---|---| | Telehealth (SC-licensed) | 3 to 7 days to consult | Same-day or next-day | Rural SC, limited specialist access | | Hepatology in-person (MUSC, Prisma) | 30 to 90 days for new patient | At or after appointment | Complex cases, biopsy needed | | Gastroenterology in-person | 14 to 45 days | At or after appointment | Patients needing endoscopy workup | | PCP with FibroScan access | 7 to 14 days | After FibroScan result | Established patients with metabolic risk |

Telehealth prescribing offers the shortest time to first prescription for straightforward cases where staging has already been completed. In-person hepatology remains the preferred route for patients who may need a liver biopsy to confirm or exclude cirrhosis before Rezdiffra is initiated. [4]

Summary of the Access Process in South Carolina

Getting Rezdiffra in South Carolina involves six concrete steps:

1. Confirm MASH with fibrosis staging (FibroScan, FIB-4, or biopsy).
2. Complete baseline labs: CMP, CBC, lipid panel, TSH, HbA1c, hepatitis serologies.
3. Schedule a consultation, in person or via SC-licensed telehealth.
4. Obtain a prescription from an MD, DO, NP, or PA licensed in SC.
5. Submit prior authorization with fibrosis staging documentation, metabolic history, and lifestyle intervention records.
6. Fill at a SC specialty pharmacy or arrange home delivery through MadrigalONE (1-833-696-2663).

Most SC patients with completed staging and labs move from consultation to first fill in 7 to 21 days. Patients facing PA denials should request a peer-to-peer review within 72 hours, citing the MAESTRO-NASH 100 mg data showing 25.9% NASH resolution at 52 weeks versus 14.2% on placebo. [3]