Resmetrom: The most promising NASH drug for fatty liver

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Resmetrom: The most promising NASH drug for fatty liver

Resmetrom: The most promising NASH drug for fatty liver, races towards market with a core compound patent expiring in 2026.

In liver cells, thyroid hormones (TH) play a pivotal role in liver function by activating their β receptors, influencing a range of health parameters from serum cholesterol and triglyceride levels to the accumulation of fat pathology in the liver.

The action of THR-β is crucial for normal liver function, including regulating mitochondrial activity, such as the breakdown of liver fat and controlling the levels of healthy mitochondria. In NASH patients, the activity level of THR-β receptors in the liver is reduced.

Resmetrom: The most promising NASH drug for fatty liver

Image 1 Source: Madrigal Pharmaceuticals Official Website

Resmetrom is a once-daily oral selective agonist of thyroid hormone receptor (THR)-β, designed to target a key underlying cause of non-alcoholic steatohepatitis (NASH). Initially developed by Roche, global development rights for this drug were acquired by Madrigal Pharmaceuticals in 2008.

On September 13, Madrigal announced that the U.S. Food and Drug Administration (FDA) has accepted its New Drug Application (NDA) for Resmetrom, intended for the treatment of adult NASH fibrosis patients, with priority review granted. The Prescription Drug User Fee Act (PDUFA) review date is set for March 14, 2024. The FDA has indicated that there are currently no plans to convene an advisory committee meeting to discuss this application.

The clinical development plan for Resmetrom comprises 18 clinical studies to support the NDA, including 12 Phase 1 studies, 2 Phase 2 studies, and 4 Phase 3 studies.

Madrigal is currently conducting 4 Phase 3 clinical trials to demonstrate the safety and efficacy of Resmetrom for NASH treatment: MAESTRO-NASH, MAESTRO-NAFLD-1, MAESTRO-NAFLD-OLE, and MAESTRO-NASH-OUTCOMES.

MAESTRO-NASH is a Phase 3 study, involving multiple centers, randomization, double-blinding, and placebo control, for NASH patients confirmed through liver biopsy. In December 2022, Madrigal announced that both daily oral doses (80mg and 100mg) of Resmetrom achieved the primary liver biopsy endpoint in MAESTRO-NASH. Multiple secondary endpoints were also met, including statistically significant reductions in atherosclerotic lipids and lipoproteins, liver enzymes, fibrosis biomarkers, and imaging tests compared to the placebo. Resmetrom demonstrated good safety and tolerability.

If Resmetrom receives FDA approval, it will become the world’s first drug to treat NASH.

Resmetrom has also been featured in Evaluate Pharma’s recent “Top 10 R&D Value Drugs Projects” globally. It is predicted that once the drug is approved, its sales could reach $2.2 billion by 2028.

Furthermore, Resmetrom has an established patent portfolio:

– Resmetrom’s core compound patent (including generic and specific compounds) has been authorized in China (CN101228135B), with a patent protection period until 2026.
– Resmetrom’s crystalline form patent is currently under review (CN108101851A, CN112638904A).
– Additionally, usage and key intermediate patents for Resmetrom have also been disclosed.