Resmetirom for MASH: Australian Clinician Guide

For the first time in the history of metabolic liver disease, there is an approved pharmacological treatment. Resmetirom (brand name Rezdiffra), approved by the FDA in March 2024 and by the European Commission in August 2025, represents a fundamental shift in how MASH is managed.

Australian clinicians are right to be paying attention — even though resmetirom is not yet approved by the TGA. Here is what you need to understand now, and why accurate liver fibrosis staging is about to become significantly more important.

Disclaimer: As of April 2026, resmetirom has not received TGA approval in Australia. This article is informational. Prescribing decisions should be based on current TGA-approved therapies and your clinical judgement.

What Is Resmetirom?

Resmetirom is a once-daily oral tablet developed by Madrigal Pharmaceuticals. It works as a selective thyroid hormone receptor-beta (THR-β) agonist — targeting the liver specifically to increase fat metabolism, reduce hepatic inflammation, and slow fibrosis progression, without the systemic cardiac or thyroid effects associated with non-selective thyroid agents.

It is indicated for non-cirrhotic MASH with moderate to advanced fibrosis — specifically fibrosis stages F2 and F3. It is not approved for cirrhotic patients (F4).

The Clinical Trial Evidence

The MAESTRO-NASH Phase 3 trial enrolled over 966 patients and demonstrated that resmetirom significantly improved MASH resolution and fibrosis outcomes at 52 weeks. Key findings:

• MASH resolution without fibrosis worsening: achieved in approximately 25–30% of resmetirom-treated patients vs ~10% placebo.

• Fibrosis improvement by ≥1 stage: achieved in approximately 24–26% vs ~14% placebo.

• Consistent efficacy regardless of concurrent GLP-1 or SGLT2 inhibitor use — important given the prevalence of these agents in the MAFLD/T2DM overlap population.

Extended data from MAESTRO-NAFLD-1 also showed meaningful liver stiffness reduction — a mean 6.7 kPa decrease from baseline (baseline mean ~25 kPa) over two years in compensated MASH cirrhosis patients, though this remains an investigational population not yet covered by the approved indication.

Why Elastography Is Central to Resmetirom

This is the critical connection for Australian clinicians and diagnostic services.

Resmetirom is approved only for F2–F3 fibrosis. That means:

• Accurate fibrosis staging is required before a patient can be considered appropriate for treatment.

• Serial elastography is required to monitor treatment response and fibrosis regression.

• Patients at F1 who progress — and patients at F4 who should not receive the drug — need to be identified reliably.

FIB-4 alone is insufficient for this level of staging precision. The Baveno VII consensus and GESA guidelines both recommend elastography for definitive staging when FIB-4 is indeterminate or when treatment decisions require confirmed staging.

Put simply: if resmetirom becomes available in Australia, the demand for reliable, accurate liver elastography will increase materially. Every hepatology practice, every gastroenterology unit, and every GP managing MAFLD patients will need access to quality elastography — not just a FIB-4 calculator.

When Might Australia Get Access?

The TGA has not publicly indicated a timeline for resmetirom approval as of April 2026. The TGA typically reviews major drugs approved by the FDA and EMA within 6–24 months of those approvals. With the FDA approval in March 2024 and European Commission approval in August 2025, a TGA submission is plausible in 2026 — but no formal approval has been announced.

PBS listing would be a further step after TGA approval, requiring PBAC evaluation of cost-effectiveness. This process can add 12–24 months to patient access timelines.

Australian clinicians interested in access to resmetirom for eligible patients should monitor TGA and PBAC announcements, and consult with Madrigal Pharmaceuticals' Australian regulatory contacts for the most current status.

Elastography Monitoring Protocol for Resmetirom Patients

The MAESTRO-NASH Phase 3 trial used liver biopsy as the primary endpoint and liver stiffness measurement (elastography) as a key secondary endpoint. In clinical practice outside a trial setting, elastography is the only validated non-invasive tool for longitudinal fibrosis monitoring in MASH patients on treatment.

The recommended monitoring protocol for patients on resmetirom or GLP-1 therapy for MASH is:

• Baseline liver stiffness measurement (LSM) before starting treatment — to confirm staging and provide a reference point for response assessment.

• Repeat elastography at 6–12 month intervals to assess treatment response.

• A change of ≥5 kPa in LSM is considered clinically meaningful per Baveno VII consensus — a reduction of ≥5 kPa indicates fibrosis regression; an increase of ≥5 kPa indicates progression requiring clinical review.

Standard liver ultrasound and blood tests (ALT/AST) are insufficient for this purpose — they do not reliably track fibrosis change over time. Elastography is the monitoring endpoint.

What to Do Now

Regardless of resmetirom's approval timeline, the clinical implication is clear: liver fibrosis staging is becoming more clinically consequential, not less. The arrival of an approved therapy means that a patient with F2–F3 MASH who is not staged properly may miss access to effective treatment. Equally, a patient with F1 or F4 disease who is incorrectly staged may receive inappropriate therapy.

For GPs prescribing GLP-1 agonists off-label for MASLD: obtain a baseline liver stiffness measurement before starting therapy. This identifies patients who need specialist referral regardless of treatment, and provides the reference point to demonstrate treatment response at 12 months.

Practices that invest now in accurate, guided liver elastography will be positioned to meet the increased staging and monitoring demand that resmetirom — and future MASH therapies — will create.