Madrigal's Resmetirom Approaches PDUFA: The First MASH Drug Could Reshape Hepatology

The FDA has until August 14 to decide whether resmetirom becomes the first approved drug for MASH (metabolic dysfunction-associated steatohepatitis) — a fatty liver disease affecting 5 million Americans with no approved treatments.

The disease nobody talks about

MASH is the severe form of MASLD (formerly NASH). Fat builds up in the liver, causes inflammation and scarring, and can progress to cirrhosis, liver failure, and liver cancer. For 30 years, the standard of care was “lose weight and exercise” — effective advice that most patients couldn’t follow.

The market is enormous. An estimated 5 million Americans have MASH with F2-F3 fibrosis — the stage resmetirom targets. Global prevalence is estimated at 100 million. Intercept Pharmaceuticals tried (and failed) with obeticholic acid. Genfit tried (and failed) with elafibranor. Madrigal is the first to reach a PDUFA date with positive Phase 3 data.

The data

The MAESTRO-NASH trial enrolled 966 patients with F2 or F3 fibrosis. At 52 weeks:

• MASH resolution: 26% of resmetirom patients vs. 14% on placebo (p < 0.001)
• Fibrosis improvement: 24% vs. 14% on placebo (p = 0.004)
• LDL cholesterol reduction: 16% (a bonus — MASH patients have cardiovascular risk)

The FDA advisory committee on August 21 will focus on two questions: whether the surrogate endpoint (fibrosis improvement) predicts clinical outcomes, and whether the cardiac safety signals (heart rate increases) are clinically meaningful.

The market

If approved, resmetirom launches into an empty market. Pricing is expected at $15,000–$20,000 per year. Peak sales estimates range from $2–4 billion. Madrigal’s market cap is currently $7.2 billion — a price that already bakes in significant expectations.

The binary risk: if the FDA issues a Complete Response Letter citing the cardiac signals, the stock could drop 40%+. If approved, the stock likely pops 10–20% on the news, then settles as investors shift focus to the launch execution.

What we’re watching

1. August 14 PDUFA: Will the FDA approve, or issue a CRL?
2. August 21 AdCom: If the FDA refers it to the advisory committee, panel sentiment is a leading indicator.
3. Launch metrics: If approved, early prescription data in Q4 2026 will tell us whether hepatologists are adopting it.
4. Competition: Akero Therapeutics (AKRO) and 89bio (ETNB) are behind with FGF21 analogs. Both report Phase 2b data later this year.

MASH is a story we’ll be following all year. The PDUFA date is the first chapter.