To Bill Sibold, “it’s hard to find a more attractive growth opportunity in biotech” than metabolic dysfunction-associated steatohepatitis (MASH). The Madrigal Pharmaceuticals CEO made the observation as the company’s Rezdiffra, the first FDA-approved MASH therapy, crossed the $1 billion mark in annual sales.
With its $431 million sales in the third quarter again topping analysts’ expectations, Rezdiffra has generated $1.1 billion in sales so far this year.
Crossing the blockbuster threshold this year was expected of Rezdiffra after the drug’s 2025 sales, at $958 million, were just one step away from the milestone. Rezdiffra stormed out of the gate following a historic FDA approval in March 2024 and has impressed Wall Street quarter after quarter.
The market for MASH—formerly known as NASH—with moderate to advanced liver scarring at fibrosis stages F2 to F3 is accelerating, “on track to grow more than 30% this year,” Sibold said on Madrigal's Q3 earnings call Tuesday. As of the end of 2025, the diagnosed F2/F3 MASH population in the U.S. had grown to about 460,000 patients, he noted.
Rezdiffra exited September with 55,850 active patients on treatment, compared to more than 29,500 a year ago, according to Sibold. That means Rezdiffra has only penetrated about 10% of the current market, while “only about 1% into the total opportunity,” he added.
Madrigal is eyeing the F4 cirrhosis market, which Sibold labeled as “a rapidly growing multi-billion-dollar market opportunity” in itself. The company’s updated F4 market estimate now puts the number of addressable patients at 360,000, up 45% from its previous calculation.
The Maestro-NASH-Outcomes trial, with a readout now expected in late 2027, could convert Rezdiffra’s current accelerated approval into a full nod and expand the drug’s reach into the F4 field.
The timing of a late-2027 readout “may give some investors pause given an incrementally lower implied overall event rate vs prior expectation,” Citi analysts noted in a report Tuesday. Nevertheless, the analysts maintained that the study has favorable odds of success based on their simulation.
To complement that study, Madrigal plans to launch another phase 3 trial in the first half of 2027 following discussions with the FDA. Called Maestro-CSPH, the huge, 2,000-subject-plus study focuses on patients with clinically significant portal hypertension.
CSPH represents an advanced stage of MASH and the primary driver of clinical decompensation, at which point the liver can no longer perform its essential functions, leading to life-threatening complications. Given its position at a critical tipping point, CSPH is “arguably where unmet need is highest,” Citi analysts said.
“Development of CSPH is a critical inflection point in the pathophysiology of compensated cirrhosis, so we are focusing this new trial where the unmet need is greatest and where preventing or delaying a clinical event is especially meaningful,” Dave Soergel, Madrigal’s chief medical officer, said on Tuesday’s call.
Madrigal is apparently putting heavy bets on the CSPH trial, given the size of the market opportunity.
“Look, we’re building a megablockbuster here, and this is the type of trial that leaders in a space do,” Sibold said. “This is a practice-shaping trial, that it’s a leapfrog study, if you will. We are going to raise the bar for the entire industry, drive the science forward, and we’re going to win in the category.”
Following the third-quarter report, Citi analysts have updated their 2027 Rezdiffra sales forecast to $2.25 billion.